4-76176503-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005506.4(SCARB2):āc.638A>Cā(p.Tyr213Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000745 in 1,611,362 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y213F) has been classified as Uncertain significance.
Frequency
Consequence
NM_005506.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.638A>C | p.Tyr213Ser | missense_variant | 5/12 | ENST00000264896.8 | |
SCARB2 | XM_047416429.1 | c.164A>C | p.Tyr55Ser | missense_variant | 5/12 | ||
SCARB2 | XM_047416430.1 | c.164A>C | p.Tyr55Ser | missense_variant | 5/12 | ||
SCARB2 | NM_001204255.2 | c.276-593A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.638A>C | p.Tyr213Ser | missense_variant | 5/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.103-23463T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1459176Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726020
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2019 | This variant is not present in population databases (ExAC no frequency). 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SCARB2-related conditions. This sequence change replaces tyrosine with serine at codon 213 of the SCARB2 protein (p.Tyr213Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at