rs752416481
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000264896.8(SCARB2):c.280C>T(p.Leu94Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000264896.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.280C>T | p.Leu94Phe | missense_variant | 3/12 | ENST00000264896.8 | NP_005497.1 | |
SCARB2 | XM_047416429.1 | c.-195C>T | 5_prime_UTR_variant | 3/12 | XP_047272385.1 | |||
SCARB2 | XM_047416430.1 | c.-195C>T | 5_prime_UTR_variant | 3/12 | XP_047272386.1 | |||
SCARB2 | NM_001204255.2 | c.276-5187C>T | intron_variant | NP_001191184.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.280C>T | p.Leu94Phe | missense_variant | 3/12 | 1 | NM_005506.4 | ENSP00000264896 | P4 | |
ENST00000651366.1 | n.103-18869G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250916Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135652
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461150Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 726876
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2024 | The c.280C>T (p.L94F) alteration is located in exon 3 (coding exon 3) of the SCARB2 gene. This alteration results from a C to T substitution at nucleotide position 280, causing the leucine (L) at amino acid position 94 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, 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 | Oct 26, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 05, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 94 of the SCARB2 protein (p.Leu94Phe). This variant is present in population databases (rs752416481, gnomAD 0.003%). 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: 531810). 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 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at