rs138955932
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005506.4(SCARB2):c.194A>T(p.Tyr65Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SCARB2
NM_005506.4 missense
NM_005506.4 missense
Scores
1
8
10
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.83
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.194A>T | p.Tyr65Phe | missense_variant | 2/12 | ENST00000264896.8 | NP_005497.1 | |
SCARB2 | NM_001204255.2 | c.194A>T | p.Tyr65Phe | missense_variant | 2/9 | NP_001191184.1 | ||
SCARB2 | XM_047416429.1 | c.-281A>T | 5_prime_UTR_variant | 2/12 | XP_047272385.1 | |||
SCARB2 | XM_047416430.1 | c.-281A>T | 5_prime_UTR_variant | 2/12 | XP_047272386.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.194A>T | p.Tyr65Phe | missense_variant | 2/12 | 1 | NM_005506.4 | ENSP00000264896.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251420Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461522Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727098
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
D;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;N;.
REVEL
Uncertain
Sift
Benign
T;.;.;.;.;T;.
Sift4G
Benign
T;.;.;.;.;T;.
Polyphen
P;.;.;.;.;.;.
Vest4
MutPred
Gain of glycosylation at T62 (P = 0.0262);Gain of glycosylation at T62 (P = 0.0262);Gain of glycosylation at T62 (P = 0.0262);Gain of glycosylation at T62 (P = 0.0262);Gain of glycosylation at T62 (P = 0.0262);Gain of glycosylation at T62 (P = 0.0262);Gain of glycosylation at T62 (P = 0.0262);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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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