7-94588701-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003919.3(SGCE):c.1285C>G(p.Gln429Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,453,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SGCE
NM_003919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Publications

0 publications found

Variant links:

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]

SGCE links:

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]

CASD1 links:

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ACMG classification

Classification was made for transcript

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=0.21412987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCE	NM_003919.3	MANE Select	c.1285C>G	p.Gln429Glu	missense	Exon 10 of 11	NP_003910.1	A0A0S2Z4P5
SGCE	NM_001346713.2		c.1393C>G	p.Gln465Glu	missense	Exon 11 of 12	NP_001333642.1	A0A2R8YGQ3
SGCE	NM_001346715.2		c.1366C>G	p.Gln456Glu	missense	Exon 10 of 11	NP_001333644.1	A0A2R8Y5J3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCE	ENST00000648936.2	MANE Select	c.1285C>G	p.Gln429Glu	missense	Exon 10 of 11	ENSP00000497130.1	O43556-1
SGCE	ENST00000428696.7	TSL:1	c.1237C>G	p.Gln413Glu	missense	Exon 9 of 11	ENSP00000397536.3	A0A2U3TZN7
SGCE	ENST00000447873.6	TSL:1	c.1258C>G	p.Gln420Glu	missense	Exon 9 of 10	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250870

AF XY:

0.0000148

show subpopulations

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:

0.00000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1453552

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33300

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.00

AC:

AN:

86072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104534

Other (OTH)

AF:

0.0000665

AC:

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Myoclonic dystonia 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

0.057

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.033

MetaRNN

Benign

0.21

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

1.8

PhyloP100

6.9

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.27

REVEL

Benign

0.28

Sift

Benign

0.20

Sift4G

Benign

0.091

Polyphen

0.0010

Vest4

0.30

MutPred

0.061

Gain of glycosylation at T460 (P = 0.097)

MVP

0.77

MPC

0.24

ClinPred

0.60

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.63

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over