rs66844808

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000231.3(SGCG):c.386-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,603,962 control chromosomes in the GnomAD database, including 11,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 975 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10505 hom. )

Consequence

SGCG
NM_000231.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.123

Publications

5 publications found

Variant links:

Genes affected

SGCG (HGNC:10809): (sarcoglycan gamma) This gene encodes gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C). [provided by RefSeq, Oct 2008]

SGCG Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2C
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics

SGCG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 13-23279329-A-G is Benign according to our data. Variant chr13-23279329-A-G is described in ClinVar as [Benign]. Clinvar id is 255601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCG	NM_000231.3 link	c.386-30A>G		intron_variant	Intron 4 of 7	ENST00000218867.4	NP_000222.2	Q13326

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCG	ENST00000218867.4 link	c.386-30A>G		intron_variant	Intron 4 of 7	1	NM_000231.3	ENSP00000218867.3		Q13326

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16047

AN:

152024

Hom.:

973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0842

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.0962

AC:

24134

AN:

250788

AF XY:

0.0967

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.0778

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.115

AC:

166690

AN:

1451820

Hom.:

10505

Cov.:

AF XY:

0.113

AC XY:

81649

AN XY:

722494

show subpopulations

African (AFR)

AF:

0.0798

AC:

2652

AN:

33252

American (AMR)

AF:

0.0804

AC:

3581

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4024

AN:

25910

East Asian (EAS)

AF:

0.000431

AC:

AN:

39402

South Asian (SAS)

AF:

0.0431

AC:

3701

AN:

85808

European-Finnish (FIN)

AF:

0.116

AC:

6135

AN:

52716

Middle Eastern (MID)

AF:

0.105

AC:

599

AN:

5726

European-Non Finnish (NFE)

AF:

0.126

AC:

139299

AN:

1104602

Other (OTH)

AF:

0.112

AC:

6682

AN:

59866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

6667

13333

20000

26666

33333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4974

9948

14922

19896

24870

<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

AF:

0.106

AC:

16059

AN:

152142

Hom.:

975

Cov.:

AF XY:

0.104

AC XY:

7760

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0844

AC:

3503

AN:

41524

American (AMR)

AF:

0.101

AC:

1544

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

552

AN:

3468

East Asian (EAS)

AF:

0.000774

AC:

AN:

5170

South Asian (SAS)

AF:

0.0371

AC:

179

AN:

4820

European-Finnish (FIN)

AF:

0.124

AC:

1313

AN:

10572

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8475

AN:

67980

Other (OTH)

AF:

0.119

AC:

250

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

735

1469

2204

2938

3673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.118

Hom.:

199

Bravo

AF:

0.104

Asia WGS

AF:

0.0280

AC:

100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2C

Benign:1

Jul 01, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.2

(source)

DANN

Benign

0.73

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over