chr7-94656044-C-T

Position:

chr7-94656044-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003919.3(SGCE):c.55G>A(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,476 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: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SGCE
NM_003919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.06

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2291877).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCE	NM_003919.3 linkuse as main transcript	c.55G>A	p.Gly19Ser	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.55G>A	p.Gly19Ser	missense_variant	1/11		NM_003919.3	ENSP00000497130.1		O43556-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

250344

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135588

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:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461360

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727034

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:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Myoclonic dystonia 11

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2022	In summary, the available evidence is currently insufficient to determine the role of this variant 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. ClinVar contains an entry for this variant (Variation ID: 285846). This missense change has been observed in individual(s) with clinical features of SGCE-related conditions (Invitae). This variant is present in population databases (rs767335346, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 19 of the SGCE protein (p.Gly19Ser). -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 28, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.0043

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0055

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

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.95

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

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.23

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

0.87

MutationAssessor

Benign

0.34

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

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.18

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

REVEL

Uncertain

0.46

Sift

Benign

0.030

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

Sift4G

Benign

0.087

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

Polyphen

0.059, 0.99

.;.;B;.;B;.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.

Vest4

0.43, 0.42, 0.54, 0.52, 0.48, 0.51

MutPred

0.30

Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);Gain of glycosylation at G19 (P = 0.0283);

MVP

0.70

MPC

0.22

ClinPred

0.19

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.21

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