1-119735333-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006623.4(PHGDH):c.682G>C(p.Gly228Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G228W) has been classified as Likely benign.
Frequency
Consequence
NM_006623.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250914Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135652
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727232
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
PHGDH deficiency Uncertain:1
This sequence change replaces glycine with arginine at codon 228 of the PHGDH protein (p.Gly228Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PHGDH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at