rs10247562

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001099401.2(SGCE):c.1294A>T(p.Ser432Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 151,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). 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 0.00022 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000081 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SGCE
NM_001099401.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Publications

20 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013756037).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000218 (33/151330) while in subpopulation EAS AF = 0.00408 (21/5142). AF 95% confidence interval is 0.00274. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 33 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099401.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGCE	NM_003919.3	MANE Select	c.1253+811A>T		intron	N/A	NP_003910.1
SGCE	NM_001099401.2		c.1294A>T	p.Ser432Cys	missense	Exon 10 of 12	NP_001092871.1
SGCE	NM_001346713.2		c.1361+811A>T		intron	N/A	NP_001333642.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SGCE	ENST00000648936.2	MANE Select	c.1253+811A>T	intron	N/A	ENSP00000497130.1
SGCE	ENST00000428696.7	TSL:1	c.1205+811A>T	intron	N/A	ENSP00000397536.3
SGCE	ENST00000447873.6	TSL:1	c.1226+811A>T	intron	N/A	ENSP00000388734.1

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

151214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00407

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000298

AC:

AN:

3360

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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: AS_VQSR

AF:

0.0000814

AC:

AN:

12290

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

8614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

176

American (AMR)

AF:

0.00

AC:

AN:

622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

296

East Asian (EAS)

AF:

0.00256

AC:

AN:

390

South Asian (SAS)

AF:

0.00

AC:

AN:

1058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

8476

Other (OTH)

AF:

0.00

AC:

AN:

522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000218

AC:

AN:

151330

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

AN XY:

73868

show subpopulations

African (AFR)

AF:

0.000242

AC:

AN:

41262

American (AMR)

AF:

0.00

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00408

AC:

AN:

5142

South Asian (SAS)

AF:

0.000211

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67792

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

1934

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

(source)

DANN

Benign

0.088

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.31

M_CAP

Benign

0.00099

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

PhyloP100

-0.044

PROVEAN

Benign

-0.47

REVEL

Benign

0.035

Sift

Benign

0.23

Sift4G

Uncertain

0.031

Vest4

0.096

MutPred

0.41

Loss of disorder (P = 0.0152)

MVP

0.076

MPC

0.19

ClinPred

0.012

GERP RS

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

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