5-156375070-T-G

Variant names:

• chr5-156375070-T-G
• rs970476
• NM_000337.6:c.192+30393T>G

Variant summary

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

The NM_000337.6(SGCD):​c.192+30393T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,890 control chromosomes in the GnomAD database, including 20,799 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 0.52 (20799 hom., cov: 31)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 6 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

LOC124901120 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.192+30393T>G		intron_variant	Intron 3 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.192+30393T>G		intron_variant	Intron 3 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.189+30393T>G		intron_variant	Intron 2 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.192+30393T>G		intron_variant	Intron 5 of 9	5		ENSP00000429378.1
SGCD	ENST00000524347.2	n.193-18683T>G		intron_variant	Intron 3 of 5	5		ENSP00000430794.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78288 AN: 151772 Hom.: 20789 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.516 AC: 78338 AN: 151890 Hom.: 20799 Cov.: 31 AF XY: 0.526 AC XY: 39081 AN XY: 74274

African (AFR) AF: 0.421 AC: 17427 AN: 41412

American (AMR) AF: 0.546 AC: 8325 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2047 AN: 3466

East Asian (EAS) AF: 0.846 AC: 4365 AN: 5158

South Asian (SAS) AF: 0.752 AC: 3624 AN: 4816

European-Finnish (FIN) AF: 0.544 AC: 5732 AN: 10532

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.516 AC: 35055 AN: 67960

Other (OTH) AF: 0.541 AC: 1137 AN: 2100

Alfa AF: 0.496 Hom.: 2873

Bravo AF: 0.508

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.75
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs970476; hg19: chr5-155802080;