rs157334

Positions:

• chr5-156690420-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000337.6(SGCD):​c.575+42884T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,086 control chromosomes in the GnomAD database, including 47,100 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 0.78 (47100 hom., cov: 32)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	NM_000337.6	c.575+42884T>A		intron_variant		ENST00000337851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000337851.9	c.575+42884T>A		intron_variant		1	NM_000337.6	P4
SGCD	ENST00000435422.7	c.572+42884T>A		intron_variant		1		A1
SGCD	ENST00000517913.5	c.575+42884T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118751 AN: 151968 Hom.: 47082 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.781 AC: 118801 AN: 152086 Hom.: 47100 Cov.: 32 AF XY: 0.787 AC XY: 58551 AN XY: 74372

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.802

Alfa AF: 0.801 Hom.: 6125

Bravo AF: 0.772

Asia WGS AF: 0.797 AC: 2775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.65

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: rs157334; hg19: chr5-156117431;