rs10247562

chr7-94597964-T-Achr7-94597964-T-Cchr7-94597964-T-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCE	NM_003919.3	c.1253+811A>T		intron_variant		ENST00000648936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCE	ENST00000648936.2	c.1253+811A>T		intron_variant			NM_003919.3	A1

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

GnomAD3 exomes AF: 0.000298 AC: 1 AN: 3360 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2030

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00256

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00408

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

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
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
MutationTaster	Benign	1.0	N;N;N;N;N;N
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

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

LitVar

Other links and lift over

dbSNP: rs10247562; hg19: chr7-94227276;