NM_003919.3:c.1253+812G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003919.3(SGCE):c.1253+812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 164,376 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 160 hom., cov: 31)

Exomes 𝑓: 0.028 ( 9 hom. )

Consequence

SGCE
NM_003919.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.87

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014960766).

BP6

Variant 7-94597963-C-T is Benign according to our data. Variant chr7-94597963-C-T is described in ClinVar as Benign. ClinVar VariationId is 235287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCE	NM_003919.3 link	c.1253+812G>A		intron_variant	Intron 9 of 10	ENST00000648936.2	NP_003910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCE	ENST00000648936.2 link	c.1253+812G>A		intron_variant	Intron 9 of 10		NM_003919.3	ENSP00000497130.1

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5396

AN:

151088

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0105

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.0313

GnomAD2 exomes

AF:

0.0171

AC:

AN:

3508

AF XY:

0.0186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.00505

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0239

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0279

AC:

367

AN:

13174

Hom.:

Cov.:

AF XY:

0.0299

AC XY:

274

AN XY:

9174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

202

American (AMR)

AF:

0.0228

AC:

AN:

658

Ashkenazi Jewish (ASJ)

AF:

0.00311

AC:

AN:

322

East Asian (EAS)

AF:

0.00

AC:

AN:

410

South Asian (SAS)

AF:

0.00401

AC:

AN:

1246

European-Finnish (FIN)

AF:

0.0161

AC:

AN:

622

Middle Eastern (MID)

AF:

0.0185

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.0357

AC:

321

AN:

8992

Other (OTH)

AF:

0.0214

AC:

AN:

560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0357

AC:

5396

AN:

151202

Hom.:

160

Cov.:

AF XY:

0.0335

AC XY:

2475

AN XY:

73820

show subpopulations

African (AFR)

AF:

0.0107

AC:

440

AN:

41162

American (AMR)

AF:

0.0348

AC:

529

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.0107

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.0309

AC:

320

AN:

10366

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0535

AC:

3627

AN:

67824

Other (OTH)

AF:

0.0310

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

253

506

759

1012

1265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0195

Hom.:

Bravo

AF:

0.0358

ExAC

AF:

0.00446

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 21, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.15

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.30

T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-1.9

PROVEAN

Benign

0.30

N;.;.;.;.

REVEL

Benign

0.012

Sift

Benign

0.75

T;.;.;.;.

Sift4G

Benign

1.0

T;.;.;.;.

Vest4

0.037

MPC

0.18

ClinPred

0.0073

GERP RS

-0.23

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over