5-156432358-T-C

Variant names:

• chr5-156432358-T-C
• rs6556615
• NM_000337.6:c.193-76243T>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.193-76243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,164 control chromosomes in the GnomAD database, including 43,565 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 0.75 (43565 hom., cov: 33)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	NM_000337.6	MANE Select	c.193-76243T>C		intron	N/A	NP_000328.2
	SGCD	NM_001128209.2		c.190-76243T>C		intron	N/A	NP_001121681.1
	SGCD	NM_172244.3		c.193-76243T>C		intron	N/A	NP_758447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000337851.9	TSL:1 MANE Select	c.193-76243T>C		intron	N/A	ENSP00000338343.4
	SGCD	ENST00000435422.7	TSL:1	c.190-76243T>C		intron	N/A	ENSP00000403003.2
	SGCD	ENST00000517913.5	TSL:5	c.193-76243T>C		intron	N/A	ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114018 AN: 152046 Hom.: 43520 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.750 AC: 114119 AN: 152164 Hom.: 43565 Cov.: 33 AF XY: 0.749 AC XY: 55749 AN XY: 74382

African (AFR) AF: 0.887 AC: 36859 AN: 41540

American (AMR) AF: 0.633 AC: 9667 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2825 AN: 3472

East Asian (EAS) AF: 0.717 AC: 3692 AN: 5148

South Asian (SAS) AF: 0.813 AC: 3927 AN: 4828

European-Finnish (FIN) AF: 0.668 AC: 7065 AN: 10578

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47449 AN: 67994

Other (OTH) AF: 0.765 AC: 1618 AN: 2116

Alfa AF: 0.724 Hom.: 50869

Bravo AF: 0.752

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.38
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6556615; hg19: chr5-155859368;