Variant: NM_000546.5(TP53):c.37C>T (p.Pro13Ser)

CA16616008

406604 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

UUID: f7698bc5-923c-4132-b1b9-68a6bd158f1b

Approved on: 2022-06-27

Published on: 2022-06-27

HGVS expressions

NM_000546.5:c.37C>T
NM_000546.5(TP53):c.37C>T (p.Pro13Ser)
NC_000017.11:g.7676558G>A
CM000679.2:g.7676558G>A
NC_000017.10:g.7579876G>A
CM000679.1:g.7579876G>A
NC_000017.9:g.7520601G>A
NG_017013.2:g.15993C>T
ENST00000269305.9:c.37C>T
ENST00000269305.8:c.37C>T
ENST00000359597.8:n.37C>T
ENST00000413465.6:n.37C>T
ENST00000420246.6:c.37C>T
ENST00000445888.6:c.37C>T
ENST00000455263.6:c.37C>T
ENST00000503591.1:c.37C>T
ENST00000505014.5:n.176C>T
ENST00000508793.5:c.37C>T
ENST00000509690.5:c.-21-1322C>T
ENST00000514944.5:c.37C>T
ENST00000604348.5:c.37C>T
ENST00000610292.4:c.-198C>T
ENST00000610538.4:c.-81C>T
ENST00000615910.4:n.37C>T
ENST00000617185.4:c.37C>T
ENST00000619485.4:c.-81C>T
ENST00000620739.4:c.-81C>T
ENST00000622645.4:c.-81C>T
ENST00000635293.1:c.-81C>T
NM_001126112.2:c.37C>T
NM_001126113.2:c.37C>T
NM_001126114.2:c.37C>T
NM_001126118.1:c.-198C>T
NM_001276695.1:c.-81C>T
NM_001276696.1:c.-81C>T
NM_001276760.1:c.-81C>T
NM_001276761.1:c.-81C>T
NM_001276695.2:c.-81C>T
NM_001276696.2:c.-81C>T
NM_001276760.2:c.-81C>T
NM_001276761.2:c.-81C>T
NM_000546.6:c.37C>T
NM_001126112.3:c.37C>T
NM_001126113.3:c.37C>T
NM_001126114.3:c.37C>T
NM_001126118.2:c.-198C>T
NM_001276695.3:c.-81C>T
NM_001276696.3:c.-81C>T
NM_001276760.3:c.-81C>T
NM_001276761.3:c.-81C>T
NM_000546.6(TP53):c.37C>T (p.Pro13Ser)

Uncertain Significance

• Met criteria codes: BS3 BP4 PS4_Supporting

• Not Met criteria codes: BS2 BS4 BS1 BP2 BP3 BP5 BP7 PS2 PS3 PS1 PP4 PP1 PP3 PM3 PM1 PM4 PM5 PM6 PM2 PVS1 BA1

Expert Panel

TP53 VCEP

Criteria Specification Information

Evidence submitted by expert panel

TP53 VCEP

Transactivation assays show retained function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644) This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). This variant has been reported in 2 probands meeting Revised Chompret criteria (PS4_Supporting; internal laboratory contributor). The TP53 VCEP allows classification of a variant as Likely Benign with two supporting benign evidence codes if there is only a single supporting pathogenic code. However, the group did not feel a classification of Likely Benign was appropriate for this variant at this time given that the BayesDel score is just below the VCEP threshold and considering the phenotypes reported in the families meeting Chompret criteria. In summary, the clinical significance of TP53 c.37C>T (p.Pro13Ser) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4, PS4_Supporting.

Met criteria codes

• BS3: Transactivation assays in yeast demonstrate a functional allele (99.75% activity, based on data from Kato et al) and there is no evidence of a dominant negative effect (DNE) and no evidence of LOF from Giacomelli et al
• BP4: Align-GVGD = C0, BayesDel = 0.1233
• PS4_Supporting: 2 individuals meeting Revised Chompret criteria from internal laboratory data = 1 point

Not Met criteria codes

• BS2: 1 woman 60+ years with no cancer in internal laboratory data
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: variant in 1 of 250,766 alleles (0.000003988)
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: variant in 1 of 250,766 alleles (0.000003988)
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: variant in 1 of 250,766 alleles (0.000003988)