rs32056

Variant names:

• chr5-156647129-G-A
• rs32056
• NM_000337.6:c.503-335G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-156647129-G-A
• chr5-156647129-G-C
• chr5-156647129-G-T

Variant summary

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

The NM_000337.6(SGCD):​c.503-335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,214 control chromosomes in the GnomAD database, including 64,372 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 0.92 (64372 hom., cov: 32)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.503-335G>A		intron_variant	Intron 6 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.503-335G>A		intron_variant	Intron 6 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.500-335G>A		intron_variant	Intron 5 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.503-335G>A		intron_variant	Intron 8 of 9	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139688 AN: 152096 Hom.: 64308 Cov.: 32

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.919 AC: 139811 AN: 152214 Hom.: 64372 Cov.: 32 AF XY: 0.922 AC XY: 68615 AN XY: 74412

African (AFR) AF: 0.974 AC: 40466 AN: 41554

American (AMR) AF: 0.934 AC: 14262 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3139 AN: 3470

East Asian (EAS) AF: 0.986 AC: 5112 AN: 5184

South Asian (SAS) AF: 0.909 AC: 4383 AN: 4824

European-Finnish (FIN) AF: 0.921 AC: 9771 AN: 10614

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59584 AN: 67986

Other (OTH) AF: 0.911 AC: 1923 AN: 2110

Alfa AF: 0.890 Hom.: 29966

Bravo AF: 0.922

Asia WGS AF: 0.928 AC: 3229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.36
PhyloP100		0.83
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: rs32056; hg19: chr5-156074139;