chr14-22775526-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_003982.4(SLC7A7):c.1013G>A(p.Gly338Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 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. G338S) has been classified as Uncertain significance.
Frequency
Consequence
NM_003982.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC7A7 | NM_003982.4 | c.1013G>A | p.Gly338Asp | missense_variant | 7/10 | ENST00000674313.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC7A7 | ENST00000674313.1 | c.1013G>A | p.Gly338Asp | missense_variant | 7/10 | NM_003982.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251292Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135804
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727200
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Lysinuric protein intolerance Pathogenic:1Uncertain:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces glycine with aspartic acid at codon 338 of the SLC7A7 protein (p.Gly338Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs386833795, ExAC 0.002%). This missense change has been observed in individual(s) with lysinuric protein intolerance (PMID: 10655553). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 56347). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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