rs267606820
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_014053.4(FLVCR1):c.361A>G(p.Asn121Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,086 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N121S) has been classified as Uncertain significance.
Frequency
Consequence
NM_014053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLVCR1 | NM_014053.4 | c.361A>G | p.Asn121Asp | missense_variant | 1/10 | ENST00000366971.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLVCR1 | ENST00000366971.9 | c.361A>G | p.Asn121Asp | missense_variant | 1/10 | 1 | NM_014053.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251126Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135806
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461872Hom.: 0 Cov.: 62 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74378
ClinVar
Submissions by phenotype
Posterior column ataxia-retinitis pigmentosa syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2012 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2021 | ClinVar contains an entry for this variant (Variation ID: 18418). 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 C15"). Experimental studies have shown that this missense change affects FLVCR1 function (PMID: 22483575). For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with posterior column ataxia retinitis pigmentosa (PMID: 21070897, 28559085, 30444160). It is commonly reported in individuals of American Mennonite ancestry (PMID: 21070897, 30444160). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 121 of the FLVCR1 protein (p.Asn121Asp). This variant is present in population databases (rs267606820, gnomAD 0.0009%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at