5-156432358-T-C

Variant summary

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

The NM_000337.6(SGCD):c.193-76243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,164 control chromosomes in the GnomAD database, including 43,565 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 0.75 (43565 hom., cov: 33)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	NM_000337.6	c.193-76243T>C		intron_variant		ENST00000337851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000337851.9	c.193-76243T>C		intron_variant		1	NM_000337.6	P4
SGCD	ENST00000435422.7	c.190-76243T>C		intron_variant		1		A1
SGCD	ENST00000517913.5	c.193-76243T>C		intron_variant		5
SGCD	ENST00000524347.2	c.*56+38493T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114018 AN: 152046 Hom.: 43520 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.750 AC: 114119 AN: 152164 Hom.: 43565 Cov.: 33 AF XY: 0.749 AC XY: 55749 AN XY: 74382

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.765

Alfa AF: 0.721 Hom.: 38656

Bravo AF: 0.752

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.2
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6556615; hg19: chr5-155859368;