2-86790400-C-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001768.7(CD8A):c.331G>A(p.Gly111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,024 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 Pathogenic (★).
Frequency
Consequence
NM_001768.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251120Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461840Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727216
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Susceptibility to respiratory infections associated with CD8alpha chain mutation Pathogenic:2
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects CD8A protein function (PMID: 21546492). 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. ClinVar contains an entry for this variant (Variation ID: 12742). This variant is also known as p.Gly90Ser. This variant has been observed in individual(s) with CD8 deficiency (PMID: 11435463, 17658607, 26563160). It is commonly reported in individuals of Spanish Gypsy ancestry (PMID: 17658607). This variant is present in population databases (rs121918660, ExAC no frequency). This sequence change replaces glycine with serine at codon 111 of the CD8A protein (p.Gly111Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at