chr7-94597964-T-G

Variant names:

• chr7-94597964-T-G
• rs10247562
• NM_003919.3:c.1253+811A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0440
• Publications: 20 publications found

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]

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]

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCE	NM_003919.3	MANE Select	c.1253+811A>C		intron	N/A	NP_003910.1
	SGCE	NM_001099401.2		c.1294A>C	p.Ser432Arg	missense	Exon 10 of 12	NP_001092871.1
	SGCE	NM_001346713.2		c.1361+811A>C		intron	N/A	NP_001333642.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCE	ENST00000648936.2	MANE Select	c.1253+811A>C		intron	N/A	ENSP00000497130.1
	SGCE	ENST00000428696.7	TSL:1	c.1205+811A>C		intron	N/A	ENSP00000397536.3
	SGCE	ENST00000447873.6	TSL:1	c.1226+811A>C		intron	N/A	ENSP00000388734.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118193 AN: 151164 Hom.: 46913 Cov.: 26

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

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.: 0 AF XY: 0.687 AC XY: 5887 AN XY: 8564

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

GnomAD4 genome AF: 0.782 AC: 118302 AN: 151280 Hom.: 46964 Cov.: 26 AF XY: 0.784 AC XY: 57865 AN XY: 73842

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

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

Submissions by phenotype

Myoclonic dystonia 11 Benign:4

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Apr 13, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.5
DANN	Benign	0.052
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.000060	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000017	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.044
PROVEAN	Benign	0.24	N
REVEL	Benign	0.018
Sift	Benign	0.49	T
Sift4G	Benign	0.43	T
Vest4		0.012
MutPred		0.32		Loss of glycosylation at S432 (P = 0.0514)
MPC		0.22
ClinPred		0.00014	T
GERP RS		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10247562; hg19: chr7-94227276; COSMIC: COSV107222529; COSMIC: COSV107222529;