rs758857853
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005506.4(SCARB2):c.1087C>A(p.His363Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SCARB2
NM_005506.4 missense
NM_005506.4 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 7.05
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.1087C>A | p.His363Asn | missense_variant | 8/12 | ENST00000264896.8 | NP_005497.1 | |
SCARB2 | NM_001204255.2 | c.658C>A | p.His220Asn | missense_variant | 5/9 | NP_001191184.1 | ||
SCARB2 | XM_047416429.1 | c.613C>A | p.His205Asn | missense_variant | 8/12 | XP_047272385.1 | ||
SCARB2 | XM_047416430.1 | c.613C>A | p.His205Asn | missense_variant | 8/12 | XP_047272386.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.1087C>A | p.His363Asn | missense_variant | 8/12 | 1 | NM_005506.4 | ENSP00000264896 | P4 | |
ENST00000651366.1 | n.102+20627G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251298Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135794
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461348Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727000
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
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1
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Action myoclonus-renal failure syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.;.;D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.;.;D;.
Sift4G
Pathogenic
D;.;.;.;.;D;.
Polyphen
D;.;.;.;.;.;.
Vest4
MutPred
Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);.;.;.;Gain of sheet (P = 0.0827);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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