rs10866716

Variant names:

• chr5-156166898-C-T
• rs10866716
• ENST00000959782.1:c.-178+42879C>T

Variant summary

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

The ENST00000959782.1(SGCD):​c.-178+42879C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,972 control chromosomes in the GnomAD database, including 25,568 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 0.56 (25568 hom., cov: 31)
• Consequence: SGCD ENST00000959782.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• 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, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women's Health, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000959782.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000959782.1		c.-178+42879C>T		intron	N/A	ENSP00000629841.1
	SGCD	ENST00000517913.5	TSL:5	c.-44+42879C>T		intron	N/A	ENSP00000429378.1	Q92629-3

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85626 AN: 151854 Hom.: 25560 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.564 AC: 85685 AN: 151972 Hom.: 25568 Cov.: 31 AF XY: 0.572 AC XY: 42449 AN XY: 74270

African (AFR) AF: 0.390 AC: 16155 AN: 41452

American (AMR) AF: 0.606 AC: 9253 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4865 AN: 5178

South Asian (SAS) AF: 0.754 AC: 3627 AN: 4810

European-Finnish (FIN) AF: 0.615 AC: 6493 AN: 10562

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41239 AN: 67914

Other (OTH) AF: 0.565 AC: 1189 AN: 2106

Alfa AF: 0.604 Hom.: 14261

Bravo AF: 0.554

Asia WGS AF: 0.769 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.55
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10866716;

hg19: chr5-155593908;