rs281875236
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PS1_ModeratePM2
The NM_001004334.4(GPR179):āc.659A>Gā(p.Tyr220Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Consequence
NM_001004334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR179 | NM_001004334.4 | c.659A>G | p.Tyr220Cys | missense_variant | 1/11 | ENST00000616987.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR179 | ENST00000616987.5 | c.659A>G | p.Tyr220Cys | missense_variant | 1/11 | 1 | NM_001004334.4 | P1 | |
GPR179 | ENST00000610867.1 | n.717A>G | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000561 AC: 14AN: 249550Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135392
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 727244
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74352
ClinVar
Submissions by phenotype
Congenital stationary night blindness 1E Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 10, 2012 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jul 26, 2023 | Criteria applied: PS4_SUP,PM2_SUP - |
not provided Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 220 of the GPR179 protein (p.Tyr220Cys). This variant is present in population databases (rs281875236, gnomAD 0.01%). This missense change has been observed in individuals with congenital stationary night blindness (PMID: 22325362, 23714322). ClinVar contains an entry for this variant (Variation ID: 31206). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects GPR179 function (PMID: 24222301). 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. - |
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at