rs756606813
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005506.4(SCARB2):c.1265C>T(p.Ala422Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A422A) has been classified as Likely benign.
Frequency
Consequence
NM_005506.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.1265C>T | p.Ala422Val | missense_variant | 11/12 | ENST00000264896.8 | |
SCARB2 | NM_001204255.2 | c.836C>T | p.Ala279Val | missense_variant | 8/9 | ||
SCARB2 | XM_047416429.1 | c.791C>T | p.Ala264Val | missense_variant | 11/12 | ||
SCARB2 | XM_047416430.1 | c.791C>T | p.Ala264Val | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.1265C>T | p.Ala422Val | missense_variant | 11/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.102+14092G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251436Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135894
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727238
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74314
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 422 of the SCARB2 protein (p.Ala422Val). This variant is present in population databases (rs756606813, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SCARB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 531799). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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