rs777270813
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005506.4(SCARB2):c.1229A>T(p.Tyr410Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SCARB2
NM_005506.4 missense
NM_005506.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 3.76
Genes affected
SCARB2 (HGNC:1665): (scavenger receptor class B member 2) The protein encoded by this gene is a type III glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is a ubiquitously expressed protein and that it is involved in the pathogenesis of HFMD (hand, foot, and mouth disease) caused by enterovirus-71 and possibly by coxsackievirus A16. Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.1229A>T | p.Tyr410Phe | missense_variant | 10/12 | ENST00000264896.8 | |
SCARB2 | NM_001204255.2 | c.800A>T | p.Tyr267Phe | missense_variant | 7/9 | ||
SCARB2 | XM_047416429.1 | c.755A>T | p.Tyr252Phe | missense_variant | 10/12 | ||
SCARB2 | XM_047416430.1 | c.755A>T | p.Tyr252Phe | missense_variant | 10/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.1229A>T | p.Tyr410Phe | missense_variant | 10/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.102+16994T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251398Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135860
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461874Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727238
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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1
Asia WGS
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1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 410 of the SCARB2 protein (p.Tyr410Phe). This variant is present in population databases (rs777270813, gnomAD 0.006%). 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: 531800). 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;N;.
REVEL
Benign
Sift
Benign
T;.;.;.;.;.;T;.
Sift4G
Benign
T;.;.;.;.;.;T;.
Polyphen
B;.;.;.;.;.;.;.
Vest4
MutPred
Gain of glycosylation at Y410 (P = 0.0953);.;Gain of glycosylation at Y410 (P = 0.0953);.;.;.;.;Gain of glycosylation at Y410 (P = 0.0953);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at