rs143558324
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_005506.4(SCARB2):c.382C>T(p.Pro128Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,098 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P128A) has been classified as Likely benign.
Frequency
Consequence
NM_005506.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.382C>T | p.Pro128Ser | missense_variant | 3/12 | ENST00000264896.8 | |
SCARB2 | XM_047416429.1 | c.-93C>T | 5_prime_UTR_variant | 3/12 | |||
SCARB2 | XM_047416430.1 | c.-93C>T | 5_prime_UTR_variant | 3/12 | |||
SCARB2 | NM_001204255.2 | c.276-5085C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.382C>T | p.Pro128Ser | missense_variant | 3/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.103-18971G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000678 AC: 17AN: 250876Hom.: 1 AF XY: 0.0000959 AC XY: 13AN XY: 135590
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461098Hom.: 2 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 726816
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2017 | The p.P128S variant (also known as c.382C>T), located in coding exon 3 of the SCARB2 gene, results from a C to T substitution at nucleotide position 382. The proline at codon 128 is replaced by serine, an amino acid with 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. - |
Action myoclonus-renal failure syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 14, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 28, 2023 | - - |
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 128 of the SCARB2 protein (p.Pro128Ser). This variant is present in population databases (rs143558324, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. 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: 462924). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Seizure Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | New York Genome Center | Feb 25, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at