chr4-76169913-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005506.4(SCARB2):āc.1067T>Cā(p.Met356Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,004 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 ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M356L) has been classified as Uncertain significance.
Frequency
Consequence
NM_005506.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.1067T>C | p.Met356Thr | missense_variant | 8/12 | ENST00000264896.8 | |
SCARB2 | NM_001204255.2 | c.638T>C | p.Met213Thr | missense_variant | 5/9 | ||
SCARB2 | XM_047416429.1 | c.593T>C | p.Met198Thr | missense_variant | 8/12 | ||
SCARB2 | XM_047416430.1 | c.593T>C | p.Met198Thr | missense_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.1067T>C | p.Met356Thr | missense_variant | 8/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.102+20647A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251322Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135816
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461790Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727202
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 11, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces methionine with threonine at codon 356 of the SCARB2 protein (p.Met356Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SCARB2-related conditions. 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. 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