rs11135380

Variant names:

• chr5-156755037-G-A
• rs11135380
• NM_000337.6:c.576-2544G>A

Variant summary

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

The NM_000337.6(SGCD):​c.576-2544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 152,158 control chromosomes in the GnomAD database, including 782 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. The gene SGCD is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.080 (782 hom., cov: 32)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• Publications: 5 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, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Specifications for SGCD are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000337.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	NM_000337.6	MANE Select	c.576-2544G>A		intron	N/A	NP_000328.2
	SGCD	NM_001128209.2		c.573-2544G>A		intron	N/A	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.576-2544G>A		intron	N/A	NP_758447.1	Q92629-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000337851.9	TSL:1 MANE Select	c.576-2544G>A		intron	N/A	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.573-2544G>A		intron	N/A	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.627-2544G>A		intron	N/A	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12133 AN: 152040 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.0777

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0800 AC: 12172 AN: 152158 Hom.: 782 Cov.: 32 AF XY: 0.0795 AC XY: 5917 AN XY: 74402

African (AFR) AF: 0.175 AC: 7244 AN: 41468

American (AMR) AF: 0.0865 AC: 1322 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3468

East Asian (EAS) AF: 0.0781 AC: 405 AN: 5188

South Asian (SAS) AF: 0.0653 AC: 315 AN: 4826

European-Finnish (FIN) AF: 0.0347 AC: 368 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2219 AN: 68014

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0466 Hom.: 434

Bravo AF: 0.0894

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		0.46
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: rs11135380; hg19: chr5-156182048;