rs10491466

Variant names:

• chr5-156669679-C-A
• rs10491466
• NM_000337.6:c.575+22143C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000337.6(SGCD):​c.575+22143C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 152,204 control chromosomes in the GnomAD database, including 75 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 0.022 (75 hom., cov: 32)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 1 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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0215 (3273/152204) while in subpopulation AFR AF = 0.046 (1911/41508). AF 95% confidence interval is 0.0443. There are 75 homozygotes in GnomAd4. There are 1538 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 75 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.575+22143C>A		intron_variant	Intron 7 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.575+22143C>A		intron_variant	Intron 7 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.572+22143C>A		intron_variant	Intron 6 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.575+22143C>A		intron_variant	Intron 9 of 9	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3264 AN: 152086 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00764

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0215 AC: 3273 AN: 152204 Hom.: 75 Cov.: 32 AF XY: 0.0207 AC XY: 1538 AN XY: 74414

African (AFR) AF: 0.0460 AC: 1911 AN: 41508

American (AMR) AF: 0.0179 AC: 274 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4824

European-Finnish (FIN) AF: 0.00764 AC: 81 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 837 AN: 68016

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0183 Hom.: 8

Bravo AF: 0.0228

Asia WGS AF: 0.0110 AC: 39 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

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: rs10491466; hg19: chr5-156096690;