rs201378067

Positions:

• chr7-94656078-C-G
• chr7-94656078-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003919.3(SGCE):​c.21G>C​(p.Trp7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W7R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGCE NM_003919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCE	NM_003919.3	c.21G>C	p.Trp7Cys	missense_variant	1/11	ENST00000648936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCE	ENST00000648936.2	c.21G>C	p.Trp7Cys	missense_variant	1/11		NM_003919.3	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250210 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135544

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.00

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: AC0 AF: 0.00 AC: 0 AN: 1459360 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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 Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myoclonic dystonia 11 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Mar 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	.;T;T;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.96	D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Benign	0.0	.;.;N;.;N;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.84	.;N;.;.;N;.;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;N;.;.;.
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	.;D;.;.;D;.;.;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D;.;.;.
Sift4G	Pathogenic	0.0	.;D;.;.;D;.;.;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D;.;.;.
Polyphen		0.94, 0.98	.;.;P;.;P;.;.;.;P;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.
Vest4		0.64, 0.62, 0.67, 0.69, 0.67, 0.61
MutPred		0.51		Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);
MVP		0.94
MPC		0.97
ClinPred		0.53	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.43

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: rs201378067; hg19: chr7-94285390;