7-94597964-T-G

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+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

Publications

20 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 487363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

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

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

GnomAD2 exomes

AF:

0.666

AC:

2237

AN:

3360

AF XY:

0.673

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 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

African (AFR)

AF:

0.892

AC:

157

AN:

176

American (AMR)

AF:

0.527

AC:

327

AN:

620

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

202

AN:

294

East Asian (EAS)

AF:

0.780

AC:

301

AN:

386

South Asian (SAS)

AF:

0.527

AC:

554

AN:

1052

European-Finnish (FIN)

AF:

0.766

AC:

455

AN:

594

Middle Eastern (MID)

AF:

0.757

AC:

115

AN:

152

European-Non Finnish (NFE)

AF:

0.698

AC:

5882

AN:

8428

Other (OTH)

AF:

0.658

AC:

342

AN:

520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

112

223

335

446

558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.782

AC:

118302

AN:

151280

Hom.:

46964

Cov.:

AF XY:

0.784

AC XY:

57865

AN XY:

73842

show subpopulations

African (AFR)

AF:

0.922

AC:

38020

AN:

41254

American (AMR)

AF:

0.728

AC:

11051

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

2640

AN:

3466

East Asian (EAS)

AF:

0.748

AC:

3847

AN:

5142

South Asian (SAS)

AF:

0.645

AC:

3059

AN:

4742

European-Finnish (FIN)

AF:

0.811

AC:

8459

AN:

10426

Middle Eastern (MID)

AF:

0.753

AC:

220

AN:

292

European-Non Finnish (NFE)

AF:

0.718

AC:

48652

AN:

67770

Other (OTH)

AF:

0.751

AC:

1578

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1198

2395

3593

4790

5988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.667

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