NM_003919.3:c.1253+814G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003919.3(SGCE):c.1253+814G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 163,474 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0084 ( 1 hom. )

Consequence

SGCE
NM_003919.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.504

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=0.01735276).

BP6

Variant 7-94597961-C-T is Benign according to our data. Variant chr7-94597961-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 586562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-94597961-C-T is described in Lovd as [Benign]. Variant chr7-94597961-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00869 (1315/151318) while in subpopulation NFE AF= 0.0127 (864/67856). AF 95% confidence interval is 0.012. There are 8 homozygotes in gnomad4. There are 609 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1315 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCE	NM_003919.3 link	c.1253+814G>A		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+814G>A		intron_variant	Intron 9 of 10		NM_003919.3	ENSP00000497130.1		O43556-1

Frequencies

GnomAD3 genomes

AF:

0.00870

AC:

1315

AN:

151208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00399

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.00567

Gnomad FIN

AF:

0.00289

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.00609

AC:

AN:

3120

Hom.:

AF XY:

0.00894

AC XY:

AN XY:

1902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00718

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00347

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00730

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00839

AC:

102

AN:

12156

Hom.:

Cov.:

AF XY:

0.00861

AC XY:

AN XY:

8480

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.00664

Gnomad4 ASJ exome

AF:

0.0211

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00433

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00926

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00869

AC:

1315

AN:

151318

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

609

AN XY:

73896

show subpopulations

Gnomad4 AFR

AF:

0.00398

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00214

Gnomad4 SAS

AF:

0.00567

Gnomad4 FIN

AF:

0.00289

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.0129

Alfa

AF:

0.00974

Hom.:

Bravo

AF:

0.00900

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0161

AC:

ExAC

AF:

0.00458

AC:

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SGCE: BP4, BS1, BS2 -

not specified

Benign:1

Dec 07, 2023

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myoclonic dystonia 11

Benign:1

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.8

DANN

Uncertain

1.0

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.63

T;T;T;T;T

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.040

N;.;.;.;.

REVEL

Benign

0.029

Sift

Pathogenic

0.0

D;.;.;.;.

Sift4G

Benign

0.51

T;.;.;.;.

Vest4

0.065

MVP

0.32

MPC

0.19

ClinPred

0.068

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