NM_000337.6:c.575+36676T>C

Variant names:

• chr5-156684212-T-C
• rs32076
• NM_000337.6:c.575+36676T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000337.6(SGCD):​c.575+36676T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 151,416 control chromosomes in the GnomAD database, including 50,973 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 0.82 (50973 hom., cov: 29)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.575+36676T>C		intron_variant	Intron 7 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.575+36676T>C		intron_variant	Intron 7 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.572+36676T>C		intron_variant	Intron 6 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.575+36676T>C		intron_variant	Intron 9 of 9	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 123863 AN: 151294 Hom.: 50948 Cov.: 29

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.818 AC: 123932 AN: 151416 Hom.: 50973 Cov.: 29 AF XY: 0.825 AC XY: 61018 AN XY: 73984

African (AFR) AF: 0.746 AC: 30740 AN: 41228

American (AMR) AF: 0.876 AC: 13331 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 2997 AN: 3464

East Asian (EAS) AF: 0.821 AC: 4208 AN: 5126

South Asian (SAS) AF: 0.888 AC: 4234 AN: 4768

European-Finnish (FIN) AF: 0.885 AC: 9312 AN: 10522

Middle Eastern (MID) AF: 0.856 AC: 250 AN: 292

European-Non Finnish (NFE) AF: 0.830 AC: 56242 AN: 67784

Other (OTH) AF: 0.828 AC: 1743 AN: 2106

Alfa AF: 0.824 Hom.: 10388

Bravo AF: 0.813

Asia WGS AF: 0.835 AC: 2906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.52
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs32076; hg19: chr5-156111223;