7-94597964-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099401.2(SGCE):​c.1294A>G​(p.Ser432Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S432C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGCE NM_001099401.2 missense
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047657043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099401.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCE	NM_003919.3	MANE Select	c.1253+811A>G		intron	N/A	NP_003910.1
	SGCE	NM_001099401.2		c.1294A>G	p.Ser432Gly	missense	Exon 10 of 12	NP_001092871.1
	SGCE	NM_001346713.2		c.1361+811A>G		intron	N/A	NP_001333642.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151216 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12290 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151332 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 73868

African (AFR) AF: 0.00 AC: 0 AN: 41264

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

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 67792

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

Alfa AF: 0.00 Hom.: 1934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.23
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.00078	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.044
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.015
Sift	Benign	0.67	T
Sift4G	Benign	0.28	T
Vest4		0.058
MutPred		0.26		Loss of stability (P = 0.0439)
MVP		0.099
MPC		0.18
ClinPred		0.026	T
GERP RS		0.11
Mutation Taster		=99/1	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;