rs10247562

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-94597964-T-A
• chr7-94597964-T-C
• chr7-94597964-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003919.3(SGCE):​c.1253+811A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 151,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000081 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGCE NM_003919.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013756037).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000218 (33/151330) while in subpopulation EAS AF = 0.00408 (21/5142). AF 95% confidence interval is 0.00274. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCE	NM_003919.3	c.1253+811A>T		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	c.1253+811A>T		intron_variant	Intron 9 of 10		NM_003919.3	ENSP00000497130.1

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151214 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00407

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000298 AC: 1 AN: 3360 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000814 AC: 1 AN: 12290 Hom.: 0 Cov.: 0 AF XY: 0.000116 AC XY: 1 AN XY: 8614

African (AFR) AF: 0.00 AC: 0 AN: 176

American (AMR) AF: 0.00 AC: 0 AN: 622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 296

East Asian (EAS) AF: 0.00256 AC: 1 AN: 390

South Asian (SAS) AF: 0.00 AC: 0 AN: 1058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8476

Other (OTH) AF: 0.00 AC: 0 AN: 522

GnomAD4 genome AF: 0.000218 AC: 33 AN: 151330 Hom.: 0 Cov.: 26 AF XY: 0.000298 AC XY: 22 AN XY: 73868

African (AFR) AF: 0.000242 AC: 10 AN: 41262

American (AMR) AF: 0.00 AC: 0 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00408 AC: 21 AN: 5142

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67792

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00 Hom.: 1934

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.1
DANN	Benign	0.088
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.31	T;T;T;T;T
M_CAP	Benign	0.00099	T
MetaRNN	Benign	0.014	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.044
PROVEAN	Benign	-0.47	N;.;.;.;.
REVEL	Benign	0.035
Sift	Benign	0.23	T;.;.;.;.
Sift4G	Uncertain	0.031	D;.;.;.;.
Vest4		0.096
MutPred		0.41		Loss of disorder (P = 0.0152);Loss of disorder (P = 0.0152);.;.;.;
MVP		0.076
MPC		0.19
ClinPred		0.012	T
GERP RS		0.11
Mutation Taster		=100/0	polymorphism

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;