rs150870503
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The ENST00000264896.8(SCARB2):āc.911A>Gā(p.Asn304Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. N304D) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000264896.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.911A>G | p.Asn304Ser | missense_variant | 7/12 | ENST00000264896.8 | NP_005497.1 | |
SCARB2 | NM_001204255.2 | c.482A>G | p.Asn161Ser | missense_variant | 4/9 | NP_001191184.1 | ||
SCARB2 | XM_047416429.1 | c.437A>G | p.Asn146Ser | missense_variant | 7/12 | XP_047272385.1 | ||
SCARB2 | XM_047416430.1 | c.437A>G | p.Asn146Ser | missense_variant | 7/12 | XP_047272386.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.911A>G | p.Asn304Ser | missense_variant | 7/12 | 1 | NM_005506.4 | ENSP00000264896 | P4 | |
ENST00000651366.1 | n.102+24961T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251304Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135804
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727246
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74368
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2020 | The p.N304S variant (also known as c.911A>G), located in coding exon 7 of the SCARB2 gene, results from an A to G substitution at nucleotide position 911. The asparagine at codon 304 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 304 of the SCARB2 protein (p.Asn304Ser). This variant is present in population databases (rs150870503, gnomAD 0.004%). 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: 462928). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCARB2 protein function. 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