rs10491466

Positions:

• chr5-156669679-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 75 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCD	NM_000337.6	c.575+22143C>A		intron_variant		ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.575+22143C>A		intron_variant		1	NM_000337.6	ENSP00000338343	P4
SGCD	ENST00000435422.7	c.572+22143C>A		intron_variant		1		ENSP00000403003	A1
SGCD	ENST00000517913.5	c.575+22143C>A		intron_variant		5		ENSP00000429378

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

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.00764

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0166 Hom.: 7

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10491466; hg19: chr5-156096690;