Variant rs758857853 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.05

Variant links:

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 links:

SCARB2 (HGNC:):

SCARB2 links:

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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 linkuse as main transcript	c.1087C>A	p.His363Asn	missense_variant	8/12	ENST00000264896.8	NP_005497.1	Q14108-1A0A024RDG6
SCARB2	NM_001204255.2 linkuse as main transcript	c.658C>A	p.His220Asn	missense_variant	5/9		NP_001191184.1	Q14108-2
SCARB2	XM_047416429.1 linkuse as main transcript	c.613C>A	p.His205Asn	missense_variant	8/12		XP_047272385.1
SCARB2	XM_047416430.1 linkuse as main transcript	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 linkuse as main transcript	c.1087C>A	p.His363Asn	missense_variant	8/12	1	NM_005506.4	ENSP00000264896.2		Q14108-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251298

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461348

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

D;.;.;.;.;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

3.8

H;.;.;.;.;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-7.0

D;.;.;.;.;D;.

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;.;.;.;.;D;.

Sift4G

Pathogenic

0.0

D;.;.;.;.;D;.

Polyphen

1.0

D;.;.;.;.;.;.

Vest4

0.85

MutPred

0.94

Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);.;.;.;Gain of sheet (P = 0.0827);

MVP

0.88

MPC

0.85

ClinPred

1.0

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.98

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over