rs751698983

chr7-94656090-C-Achr7-94656090-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003919.3(SGCE):c.9G>T(p.Leu3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L3L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SGCE NM_003919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18021044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCE	NM_003919.3	c.9G>T	p.Leu3Phe	missense_variant	1/11	ENST00000648936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCE	ENST00000648936.2	c.9G>T	p.Leu3Phe	missense_variant	1/11		NM_003919.3	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249958 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135444

Gnomad AFR exome AF: 0.00

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: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453006 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723546

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	19
Dann	Benign	0.93
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.79	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
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.18	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	0.82	D
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.71	T
Polyphen		0.0	.;.;B;.;B;.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;B;.;.;.
Vest4		0.24, 0.23, 0.29, 0.25, 0.31, 0.24
MutPred		0.26		Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);Loss of disorder (P = 0.1228);
MVP		0.82
MPC		0.79
ClinPred		0.30	T
GERP RS		-0.049
Varity_R		0.10
gMVP		0.096

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: rs751698983; hg19: chr7-94285402;