rs773017713

Variant names:

• chr4-76179549-C-A
• rs773017713
• NM_005506.4:c.580G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-76179549-C-A
• chr4-76179549-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005506.4(SCARB2):​c.580G>T​(p.Asp194Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D194N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCARB2 NM_005506.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 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 2 ACMG points.

• 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.580G>T	p.Asp194Tyr	missense_variant	Exon 4 of 12	ENST00000264896.8	NP_005497.1
SCARB2	XM_047416429.1	c.106G>T	p.Asp36Tyr	missense_variant	Exon 4 of 12		XP_047272385.1
SCARB2	XM_047416430.1	c.106G>T	p.Asp36Tyr	missense_variant	Exon 4 of 12		XP_047272386.1
SCARB2	NM_001204255.2	c.276-3639G>T		intron_variant	Intron 2 of 8		NP_001191184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.580G>T	p.Asp194Tyr	missense_variant	Exon 4 of 12	1	NM_005506.4	ENSP00000264896.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	T;.;.;.;.;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Uncertain	2.9	M;.;.;.;.;.
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.1	D;.;.;.;.;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.012	D;.;.;.;.;.
Sift4G	Uncertain	0.0080	D;.;.;.;.;.
Polyphen		0.98	D;.;.;.;.;.
Vest4		0.35
MutPred		0.46		Loss of solvent accessibility (P = 0.0052);.;Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);.;Loss of solvent accessibility (P = 0.0052);
MVP		0.76
MPC		0.90
ClinPred		0.90	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.59
gMVP		0.81
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs773017713; hg19: chr4-77100702;