7-94623440-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.391-43A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,238,746 control chromosomes in the GnomAD database, including 13,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1379 hom., cov: 32)

Exomes 𝑓: 0.14 ( 11790 hom. )

Consequence

SGCE
NM_003919.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.185

Publications

3 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 (BayesDel_noAF=-0.54).

BP6

Variant 7-94623440-T-G is Benign according to our data. Variant chr7-94623440-T-G is described in ClinVar as Benign. ClinVar VariationId is 259198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCE	NM_003919.3 link	c.391-43A>C		intron_variant	Intron 3 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.391-43A>C		intron_variant	Intron 3 of 10		NM_003919.3	ENSP00000497130.1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17777

AN:

152024

Hom.:

1374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.114

GnomAD2 exomes

AF:

0.162

AC:

35425

AN:

218822

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.138

AC:

149828

AN:

1086604

Hom.:

11790

Cov.:

AF XY:

0.142

AC XY:

78930

AN XY:

556652

show subpopulations

African (AFR)

AF:

0.0207

AC:

508

AN:

24500

American (AMR)

AF:

0.168

AC:

6750

AN:

40282

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3091

AN:

23148

East Asian (EAS)

AF:

0.235

AC:

8773

AN:

37266

South Asian (SAS)

AF:

0.239

AC:

17580

AN:

73634

European-Finnish (FIN)

AF:

0.207

AC:

10837

AN:

52462

Middle Eastern (MID)

AF:

0.139

AC:

672

AN:

4824

European-Non Finnish (NFE)

AF:

0.122

AC:

95412

AN:

782888

Other (OTH)

AF:

0.130

AC:

6205

AN:

47600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6511

13022

19532

26043

32554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2954

5908

8862

11816

14770

<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:

0.117

AC:

17770

AN:

152142

Hom.:

1379

Cov.:

AF XY:

0.124

AC XY:

9255

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0253

AC:

1050

AN:

41556

American (AMR)

AF:

0.153

AC:

2328

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

492

AN:

3468

East Asian (EAS)

AF:

0.228

AC:

1182

AN:

5180

South Asian (SAS)

AF:

0.244

AC:

1177

AN:

4820

European-Finnish (FIN)

AF:

0.215

AC:

2278

AN:

10580

Middle Eastern (MID)

AF:

0.137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.130

AC:

8847

AN:

67962

Other (OTH)

AF:

0.113

AC:

238

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

784

1569

2353

3138

3922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.122

Hom.:

243

Bravo

AF:

0.108

Asia WGS

AF:

0.193

AC:

670

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 24. Only high quality variants are reported. -

Myoclonic dystonia 11

Benign:2

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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