rs751698983

Variant names:

• chr7-94656090-C-A
• rs751698983
• NM_003919.3:c.9G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-94656090-C-A
• chr7-94656090-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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
• Publications: 1 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]

PEG10 (HGNC:14005): (paternally expressed 10) This is a paternally expressed imprinted gene that is thought to have been derived from the Ty3/Gypsy family of retrotransposons. It contains two overlapping open reading frames, RF1 and RF2, and expresses two proteins: a shorter, gag-like protein (with a CCHC-type zinc finger domain) from RF1; and a longer, gag/pol-like fusion protein (with an additional aspartic protease motif) from RF1/RF2 by -1 translational frameshifting (-1 FS). While -1 FS has been observed in RNA viruses and transposons in both prokaryotes and eukaryotes, this gene represents the first example of -1 FS in a eukaryotic cellular gene. This gene is highly conserved across mammalian species and retains the heptanucleotide (GGGAAAC) and pseudoknot elements required for -1 FS. It is expressed in adult and embryonic tissues (most notably in placenta) and reported to have a role in cell proliferation, differentiation and apoptosis. Overexpression of this gene has been associated with several malignancies, such as hepatocellular carcinoma and B-cell lymphocytic leukemia. Knockout mice lacking this gene showed early embryonic lethality with placental defects, indicating the importance of this gene in embryonic development. Additional isoforms resulting from alternatively spliced transcript variants, and use of upstream non-AUG (CUG) start codon have been reported for this gene. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
SGCE	NM_003919.3	c.9G>T	p.Leu3Phe	missense_variant	Exon 1 of 11	ENST00000648936.2	NP_003910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCE	ENST00000648936.2	c.9G>T	p.Leu3Phe	missense_variant	Exon 1 of 11		NM_003919.3	ENSP00000497130.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249958 AF XY: 0.00000738

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104028

Other (OTH) AF: 0.00 AC: 0 AN: 60124

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
DEOGEN2	Benign	0.0053	.;T;T;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.
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
MutationAssessor	Benign	0.0	.;.;N;.;N;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PhyloP100		0.13
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.38	.;N;.;.;N;.;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;N;.;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.10	.;T;.;.;T;.;.;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.
Sift4G	Pathogenic	0.0	.;D;.;.;D;.;.;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D;.;.;.
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
PromoterAI		-0.0068	Neutral
Varity_R		0.10
gMVP		0.096
Mutation Taster		=91/9	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: rs751698983; hg19: chr7-94285402;