rs886041079

Variant names:

• chr4-76163233-TGGATC-GGTGCATGCAT
• rs886041079
• NM_005506.4:c.1385_1390delGATCCAinsATGCATGCACC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_005506.4(SCARB2):​c.1385_1390delGATCCAinsATGCATGCACC​(p.Gly462AspfsTer34) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. G462G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCARB2 NM_005506.4 frameshift, missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.03
• Publications: 3 publications found

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]

SCARB2 Gene-Disease associations (from GenCC):

• action myoclonus-renal failure syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Unverricht-Lundborg syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286074 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0362 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.1385_1390delGATCCAinsATGCATGCACC	p.Gly462AspfsTer34	frameshift_variant, missense_variant	Exon 11 of 12	ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.956_961delGATCCAinsATGCATGCACC	p.Gly319AspfsTer34	frameshift_variant, missense_variant	Exon 8 of 9		NP_001191184.1
SCARB2	XM_047416429.1	c.911_916delGATCCAinsATGCATGCACC	p.Gly304AspfsTer34	frameshift_variant, missense_variant	Exon 11 of 12		XP_047272385.1
SCARB2	XM_047416430.1	c.911_916delGATCCAinsATGCATGCACC	p.Gly304AspfsTer34	frameshift_variant, missense_variant	Exon 11 of 12		XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.1385_1390delGATCCAinsATGCATGCACC	p.Gly462AspfsTer34	frameshift_variant, missense_variant	Exon 11 of 12	1	NM_005506.4	ENSP00000264896.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Action myoclonus-renal failure syndrome Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=7/193	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886041079; hg19: chr4-77084386;