chr5-156287334-T-C

Variant names:

• chr5-156287334-T-C
• rs10052410
• ENST00000517913.5:c.-43-42200T>C

Variant summary

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

The ENST00000517913.5(SGCD):​c.-43-42200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,866 control chromosomes in the GnomAD database, including 13,957 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 0.41 (13957 hom., cov: 32)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517913.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000517913.5	TSL:5	c.-43-42200T>C		intron	N/A	ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62415 AN: 151750 Hom.: 13951 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.411 AC: 62469 AN: 151866 Hom.: 13957 Cov.: 32 AF XY: 0.405 AC XY: 30046 AN XY: 74194

African (AFR) AF: 0.571 AC: 23635 AN: 41390

American (AMR) AF: 0.383 AC: 5833 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1156 AN: 3466

East Asian (EAS) AF: 0.0836 AC: 432 AN: 5168

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4814

European-Finnish (FIN) AF: 0.398 AC: 4198 AN: 10540

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.368 AC: 24966 AN: 67928

Other (OTH) AF: 0.377 AC: 796 AN: 2112

Alfa AF: 0.380 Hom.: 32685

Bravo AF: 0.418

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.052
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10052410; hg19: chr5-155714344;