Variant: NM_001126112.2(TP53):c.943T>A (p.Ser315Thr)

CA000506

185212 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 5193a588-32d8-40ff-a27b-172881bdd1f0

HGVS expressions

NM_001126112.2:c.943T>A
NM_001126112.2(TP53):c.943T>A (p.Ser315Thr)
ENST00000269305.9:c.943T>A
ENST00000269305.8:c.943T>A
ENST00000359597.8:n.943T>A
ENST00000413465.6:n.782+596T>A
ENST00000420246.6:c.943T>A
ENST00000445888.6:c.943T>A
ENST00000455263.6:c.943T>A
ENST00000504290.5:c.547T>A
ENST00000504937.5:c.547T>A
ENST00000509690.5:c.547T>A
ENST00000510385.5:c.547T>A
ENST00000576024.1:n.3T>A
ENST00000610292.4:c.826T>A
ENST00000610538.4:c.826T>A
ENST00000610623.4:c.466T>A
ENST00000615910.4:n.910T>A
ENST00000617185.4:c.943T>A
ENST00000618944.4:c.466T>A
ENST00000619186.4:c.466T>A
ENST00000619485.4:c.826T>A
ENST00000620739.4:c.826T>A
ENST00000622645.4:c.826T>A
ENST00000635293.1:c.826T>A
NM_000546.5:c.943T>A
NM_001126113.2:c.943T>A
NM_001126114.2:c.943T>A
NM_001126115.1:c.547T>A
NM_001126116.1:c.547T>A
NM_001126117.1:c.547T>A
NM_001126118.1:c.826T>A
NM_001276695.1:c.826T>A
NM_001276696.1:c.826T>A
NM_001276697.1:c.466T>A
NM_001276698.1:c.466T>A
NM_001276699.1:c.466T>A
NM_001276760.1:c.826T>A
NM_001276761.1:c.826T>A
NM_001276695.2:c.826T>A
NM_001276696.2:c.826T>A
NM_001276697.2:c.466T>A
NM_001276698.2:c.466T>A
NM_001276699.2:c.466T>A
NM_001276760.2:c.826T>A
NM_001276761.2:c.826T>A
NM_000546.6:c.943T>A
NM_001126112.3:c.943T>A
NM_001126113.3:c.943T>A
NM_001126114.3:c.943T>A
NM_001126115.2:c.547T>A
NM_001126116.2:c.547T>A
NM_001126117.2:c.547T>A
NM_001126118.2:c.826T>A
NM_001276695.3:c.826T>A
NM_001276696.3:c.826T>A
NM_001276697.3:c.466T>A
NM_001276698.3:c.466T>A
NM_001276699.3:c.466T>A
NM_001276760.3:c.826T>A
NM_001276761.3:c.826T>A
NC_000017.11:g.7673585A>T
CM000679.2:g.7673585A>T
NC_000017.10:g.7576903A>T
CM000679.1:g.7576903A>T
NC_000017.9:g.7517628A>T
NG_017013.2:g.18966T>A

Likely Benign

• Met criteria codes: BP4 BS3

• Not Met criteria codes: BP2 BA1 PP1 PP3 PM6 PM2 PM1 BS4 BS1 BS2 PS2 PS4 PS3

Expert Panel

TP53 VCEP

Criteria Specification Information

Evidence submitted by expert panel

TP53 VCEP

This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). Additionally, 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). In summary, TP53 c.943T>A; p.Ser315Thr meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BP4 and BS3.

Met criteria codes

• BP4: BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). no effect on splicing (varSEAK program)
• BS3: 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).

Not Met criteria codes

• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: gnomAD highest MAF 0.009%
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4).
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: Present in gnomAD
• PM1: Not a known hotspot
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: gnomAD highest MAF 0.009%; sub-population allele count (only 3 alleles)
• BS2: Not identified in FLOSSIES database
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: Not identified in probands in the literature
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2020-09-04

Published on: 2021-06-16