Genetic Variant NM_003919.3:c.1253+814G>A (chr7-94597961-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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=0.01735276).

BP6

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

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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1315 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGCE	NM_003919.3	MANE Select	c.1253+814G>A		intron	N/A	NP_003910.1
SGCE	NM_001099401.2		c.1297G>A	p.Asp433Asn	missense	Exon 10 of 12	NP_001092871.1
SGCE	NM_001346713.2		c.1361+814G>A		intron	N/A	NP_001333642.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SGCE	ENST00000648936.2	MANE Select	c.1253+814G>A	intron	N/A	ENSP00000497130.1
SGCE	ENST00000428696.7	TSL:1	c.1205+814G>A	intron	N/A	ENSP00000397536.3
SGCE	ENST00000447873.6	TSL:1	c.1226+814G>A	intron	N/A	ENSP00000388734.1

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

GnomAD2 exomes

AF:

0.00609

AC:

AN:

3120

AF XY:

0.00894

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 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

African (AFR)

AF:

0.0174

AC:

AN:

172

American (AMR)

AF:

0.00664

AC:

AN:

602

Ashkenazi Jewish (ASJ)

AF:

0.0211

AC:

AN:

284

East Asian (EAS)

AF:

0.00

AC:

AN:

392

South Asian (SAS)

AF:

0.00433

AC:

AN:

1156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

588

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.00926

AC:

AN:

8318

Other (OTH)

AF:

0.0100

AC:

AN:

500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00869

AC:

1315

AN:

151318

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

609

AN XY:

73896

show subpopulations

African (AFR)

AF:

0.00398

AC:

164

AN:

41232

American (AMR)

AF:

0.00869

AC:

132

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3464

East Asian (EAS)

AF:

0.00214

AC:

AN:

5146

South Asian (SAS)

AF:

0.00567

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00289

AC:

AN:

10366

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0127

AC:

864

AN:

67856

Other (OTH)

AF:

0.0129

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

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

May 01, 2025

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.8

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.63

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

PhyloP100

-0.50

PROVEAN

Benign

-0.040

REVEL

Benign

0.029

Sift

Pathogenic

0.0

Sift4G

Benign

0.51

Vest4

0.065

MVP

0.32

MPC

0.19

ClinPred

0.068

GERP RS

0.11

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over