dbSNP rs9314059: SGCD:c.576-50257A>G (chr5-156707324-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000337.6(SGCD):c.576-50257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 152,264 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 155 hom., cov: 33)

Consequence

SGCD
NM_000337.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.432

Publications

1 publications found

Variant links:

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD 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 2F
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy 1L
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

SGCD links:

ENSG00000254163 (HGNC:):

ENSG00000254163 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6 link	c.576-50257A>G		intron_variant	Intron 7 of 8	ENST00000337851.9	NP_000328.2	Q92629-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SGCD	ENST00000337851.9 link	c.576-50257A>G	intron_variant	Intron 7 of 8	1	NM_000337.6	ENSP00000338343.4	Q92629-2
SGCD	ENST00000435422.7 link	c.573-50257A>G	intron_variant	Intron 6 of 7	1		ENSP00000403003.2	Q92629-1
SGCD	ENST00000517913.5 link	c.576-50257A>G	intron_variant	Intron 9 of 9	5		ENSP00000429378.1	Q92629-3
ENSG00000254163	ENST00000520705.1 link	n.243-3049T>C	intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4664

AN:

152146

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0721

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0307

AC:

4674

AN:

152264

Hom.:

155

Cov.:

AF XY:

0.0298

AC XY:

2217

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0722

AC:

2997

AN:

41526

American (AMR)

AF:

0.0200

AC:

306

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.0358

AC:

173

AN:

4828

European-Finnish (FIN)

AF:

0.00772

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0137

AC:

932

AN:

68018

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

230

460

689

919

1149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0279

Hom.:

Bravo

AF:

0.0326

Asia WGS

AF:

0.0210

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.69

PhyloP100

-0.43

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over