Variant rs773531358 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003919.3(SGCE):c.77G>A(p.Ser26Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SGCE
NM_003919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

Variant links:

Genes affected

SGCE (HGNC:10808): (sarcoglycan epsilon) This gene encodes the epsilon member of the sarcoglycan family. Sarcoglycans are transmembrane proteins that are components of the dystrophin-glycoprotein complex, which link the actin cytoskeleton to the extracellular matrix. Unlike other family members which are predominantly expressed in striated muscle, the epsilon sarcoglycan is more broadly expressed. Mutations in this gene are associated with myoclonus-dystonia syndrome. This gene is imprinted, with preferential expression from the paternal allele. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A pseudogene associated with this gene is located on chromosome 2. [provided by RefSeq, Oct 2016]

SGCE links:

SGCE (HGNC:):

SGCE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23846492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCE	NM_003919.3 linkuse as main transcript	c.77G>A	p.Ser26Asn	missense_variant	1/11	ENST00000648936.2	NP_003910.1	O43556-1A0A0S2Z4P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCE	ENST00000648936.2 linkuse as main transcript	c.77G>A	p.Ser26Asn	missense_variant	1/11		NM_003919.3	ENSP00000497130.1		O43556-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249778

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135364

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460290

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726586

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myoclonic dystonia 11

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 30, 2019

In summary, this variant has uncertain impact on SGCE function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a SGCE-related disease. This variant is present in population databases (rs773531358, ExAC 0.006%). This sequence change replaces serine with asparagine at codon 26 of the SGCE protein (p.Ser26Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.015

.;T;T;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.027

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.83

T;T;.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.24

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.90

MutationAssessor

Benign

0.34

.;.;N;.;N;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.68

.;N;.;.;N;.;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;N;.;.;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.016

.;D;.;.;D;.;.;D;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D;.;.;.

Sift4G

Benign

0.36

.;T;.;.;T;.;.;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.

Polyphen

0.14, 0.27, 0.53

.;.;B;.;B;.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;P;.;.;.

Vest4

0.58, 0.56, 0.55, 0.51, 0.58, 0.50

MutPred

0.15

Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);Loss of phosphorylation at S26 (P = 0.0241);

MVP

0.78

MPC

0.26

ClinPred

0.41

GERP RS

3.1

Varity_R

0.22

gMVP

0.59

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