NM_003919.3:c.1253+811A>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003919.3(SGCE):c.1253+811A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 163,502 control chromosomes in the GnomAD database, including 49,920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46964 hom., cov: 26)

Exomes 𝑓: 0.68 ( 2956 hom. )

Consequence

SGCE
NM_003919.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0440

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:

CASD1 (HGNC:16014): (CAS1 domain containing 1) Enables N-acetylneuraminate 7-O(or 9-O)-acetyltransferase activity. Involved in carbohydrate metabolic process. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

CASD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6818324E-6).

BP6

Variant 7-94597964-T-G is Benign according to our data. Variant chr7-94597964-T-G is described in ClinVar as [Benign]. Clinvar id is 487363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-94597964-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCE	NM_003919.3 link	c.1253+811A>C		intron_variant	Intron 9 of 10	ENST00000648936.2	NP_003910.1	O43556-1A0A0S2Z4P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCE	ENST00000648936.2 link	c.1253+811A>C		intron_variant	Intron 9 of 10		NM_003919.3	ENSP00000497130.1		O43556-1

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

118193

AN:

151164

Hom.:

46913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

0.858

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.811

Gnomad MID

AF:

0.729

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.750

GnomAD3 exomes

AF:

0.666

AC:

2237

AN:

3360

Hom.:

748

AF XY:

0.673

AC XY:

1367

AN XY:

2030

show subpopulations

Gnomad AFR exome

AF:

0.964

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.705

Gnomad EAS exome

AF:

0.694

Gnomad SAS exome

AF:

0.559

Gnomad FIN exome

AF:

0.778

Gnomad NFE exome

AF:

0.689

Gnomad OTH exome

AF:

0.739

GnomAD4 exome

AF:

0.682

AC:

8335

AN:

12222

Hom.:

2956

Cov.:

AF XY:

0.687

AC XY:

5887

AN XY:

8564

show subpopulations

Gnomad4 AFR exome

AF:

0.892

Gnomad4 AMR exome

AF:

0.527

Gnomad4 ASJ exome

AF:

0.687

Gnomad4 EAS exome

AF:

0.780

Gnomad4 SAS exome

AF:

0.527

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.698

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.782

AC:

118302

AN:

151280

Hom.:

46964

Cov.:

AF XY:

0.784

AC XY:

57865

AN XY:

73842

show subpopulations

Gnomad4 AFR

AF:

0.922

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.762

Gnomad4 EAS

AF:

0.748

Gnomad4 SAS

AF:

0.645

Gnomad4 FIN

AF:

0.811

Gnomad4 NFE

AF:

0.718

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.667

Hom.:

1934

Bravo

AF:

0.784

TwinsUK

AF:

0.712

AC:

2639

ALSPAC

AF:

0.716

AC:

2759

ExAC

AF:

0.524

AC:

4307

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Myoclonic dystonia 11

Benign:4

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 13, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.5

DANN

Benign

0.052

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.28

T;T;T;T;T

MetaRNN

Benign

0.0000017

T;T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.24

N;.;.;.;.

REVEL

Benign

0.018

Sift

Benign

0.49

T;.;.;.;.

Sift4G

Benign

0.43

T;.;.;.;.

Vest4

0.012

MutPred

0.32

Loss of glycosylation at S432 (P = 0.0514);Loss of glycosylation at S432 (P = 0.0514);.;.;.;

MPC

0.22

ClinPred

0.00014

GERP RS

0.11

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