7-94597963-C-T

Position:

• chr7-94597963-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001099401.2(SGCE):​c.1295G>A​(p.Ser432Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 164,376 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S432R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.036 (160 hom., cov: 31)
  • Exomes 𝑓: 0.028 (9 hom.)
• Consequence: SGCE NM_001099401.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.87

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]

SGCE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014960766).
• BP6: Variant 7-94597963-C-T is Benign according to our data. Variant chr7-94597963-C-T is described in ClinVar as [Benign]. Clinvar id is 235287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-94597963-C-T is described in Lovd as [Benign]. Variant chr7-94597963-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCE	NM_003919.3	c.1253+812G>A		intron_variant		ENST00000648936.2	NP_003910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCE	ENST00000648936.2	c.1253+812G>A		intron_variant			NM_003919.3	ENSP00000497130.1

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5396 AN: 151088 Hom.: 160 Cov.: 31

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0313

GnomAD3 exomes AF: 0.0171 AC: 60 AN: 3508 Hom.: 1 AF XY: 0.0186 AC XY: 39 AN XY: 2092

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.00505

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00318

Gnomad FIN exome AF: 0.0144

Gnomad NFE exome AF: 0.0239

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0279 AC: 367 AN: 13174 Hom.: 9 Cov.: 0 AF XY: 0.0299 AC XY: 274 AN XY: 9174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.00311

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00401

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.0357 AC: 5396 AN: 151202 Hom.: 160 Cov.: 31 AF XY: 0.0335 AC XY: 2475 AN XY: 73820

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0107

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0310

Alfa AF: 0.0195 Hom.: 9

Bravo AF: 0.0358

ExAC AF: 0.00446 AC: 46

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 21, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.15
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00017	N
LIST_S2	Benign	0.30	T;T;T;T;T
MetaRNN	Benign	0.0015	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.30	N;.;.;.;.
REVEL	Benign	0.012
Sift	Benign	0.75	T;.;.;.;.
Sift4G	Benign	1.0	T;.;.;.;.
Vest4		0.037
MPC		0.18
ClinPred		0.0073	T
GERP RS		-0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs559235992; hg19: chr7-94227275;