Genetic Variant SGCG:c.505+46T>A (chr13-23279524-T-A) – ACMG Classification: Benign (-20 pts)

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.505+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,590,500 control chromosomes in the GnomAD database, including 777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 64 hom., cov: 32)

Exomes 𝑓: 0.026 ( 713 hom. )

Consequence

SGCG
NM_000231.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.498

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 links:

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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=-0.86).

BP6

Variant 13-23279524-T-A is Benign according to our data. Variant chr13-23279524-T-A is described in ClinVar as [Benign]. Clinvar id is 255602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-23279524-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCG	NM_000231.3 link	c.505+46T>A		intron_variant	Intron 5 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.505+46T>A		intron_variant	Intron 5 of 7	1	NM_000231.3	ENSP00000218867.3		Q13326

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3313

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0797

Gnomad SAS

AF:

0.0461

Gnomad FIN

AF:

0.0470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0226

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.0320

AC:

7865

AN:

245708

AF XY:

0.0320

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0437

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0721

Gnomad FIN exome

AF:

0.0479

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0224

GnomAD4 exome

AF:

0.0261

AC:

37513

AN:

1438376

Hom.:

713

Cov.:

AF XY:

0.0265

AC XY:

18992

AN XY:

716194

show subpopulations

African (AFR)

AF:

0.00298

AC:

AN:

32896

American (AMR)

AF:

0.0414

AC:

1829

AN:

44176

Ashkenazi Jewish (ASJ)

AF:

0.00884

AC:

227

AN:

25678

East Asian (EAS)

AF:

0.0914

AC:

3563

AN:

38992

South Asian (SAS)

AF:

0.0448

AC:

3804

AN:

84880

European-Finnish (FIN)

AF:

0.0476

AC:

2484

AN:

52204

Middle Eastern (MID)

AF:

0.00738

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0218

AC:

23907

AN:

1094534

Other (OTH)

AF:

0.0263

AC:

1559

AN:

59322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1707

3414

5121

6828

8535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0218

AC:

3313

AN:

152124

Hom.:

Cov.:

AF XY:

0.0229

AC XY:

1705

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00390

AC:

162

AN:

41510

American (AMR)

AF:

0.0268

AC:

410

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3470

East Asian (EAS)

AF:

0.0798

AC:

412

AN:

5160

South Asian (SAS)

AF:

0.0462

AC:

222

AN:

4810

European-Finnish (FIN)

AF:

0.0470

AC:

498

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0226

AC:

1534

AN:

67986

Other (OTH)

AF:

0.0185

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

146

291

437

582

728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.76

PhyloP100

-0.50

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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chr13-23279524-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over