rs886041077
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005506.4(SCARB2):c.1016_1017insT(p.His341ThrfsTer7) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SCARB2
NM_005506.4 frameshift
NM_005506.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.66
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 Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-76169963-G-GA is Pathogenic according to our data. Variant chr4-76169963-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 268142.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.1016_1017insT | p.His341ThrfsTer7 | frameshift_variant | 8/12 | ENST00000264896.8 | |
SCARB2 | NM_001204255.2 | c.587_588insT | p.His198ThrfsTer7 | frameshift_variant | 5/9 | ||
SCARB2 | XM_047416429.1 | c.542_543insT | p.His183ThrfsTer7 | frameshift_variant | 8/12 | ||
SCARB2 | XM_047416430.1 | c.542_543insT | p.His183ThrfsTer7 | frameshift_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.1016_1017insT | p.His341ThrfsTer7 | frameshift_variant | 8/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.102+20700dup | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251236Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135772
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727152
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2020 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29605618, 23225201) - |
Action myoclonus-renal failure syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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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