NM_001354304.2:c.968C>T

CA16020906

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: 53ed0d17-3146-4fae-9046-a434d4c41d0e

Approved on: 2020-06-25

Published on: 2020-06-25

HGVS expressions

NM_001354304.2:c.968C>T
NM_000277.1:c.968C>T
NM_000277.2:c.968C>T
NM_001354304.1:c.968C>T
NM_000277.3:c.968C>T
ENST00000307000.7:c.953C>T
ENST00000549247.6:n.727C>T
ENST00000551114.2:n.630C>T
ENST00000553106.5:c.968C>T
ENST00000635477.1:n.74-2465C>T
ENST00000635528.1:n.483C>T
NC_000012.12:g.102846896G>A
CM000674.2:g.102846896G>A
NC_000012.11:g.103240674G>A
CM000674.1:g.103240674G>A
NC_000012.10:g.101764804G>A
NG_008690.1:g.75707C>T
NG_008690.2:g.116515C>T

Uncertain Significance

• Met criteria codes: PP3 PP4 PM2 PM3_Supporting

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.968C>T (p.Thr323Ile) variant in PAH meets criteria to be classified as uncertain significance due to insufficient evidence. PAH-specific ACMG/AMP criteria applied: PM2: Absent from population databases (1000 Genomes, ExAC). PP3: Computational prediction tools suggest that the c.968C>T variant is damaging to protein function. Evolutionarily conserved. PP4: Patient has classic PKU (PMID:24350308). PM3_Supporting: Found to co-occur with p.R408W in one patient with classic PKU, but no additional studies to demonstrate phase of variants. No other PAH variants identified in patient (PMID:24350308). Undefined BH4 responsiveness (PMID:24350308).

Met criteria codes

• PP3: Predicted to be damaging by SIFT, PolyPhen, and MutTaster. Evolutionarily conserved.
• PP4: Patient has classic PKU
• PM2: Absent in all databases
• PM3_Supporting: In Bik-Multanowski et al, found to co-occur with p.R408W (well-established pathogenic variant) in patient with classic PKU. There are not parental studies to demonstrate phase of the variants