5-156356284-C-T

Variant names:

• chr5-156356284-C-T
• rs1394608
• NM_000337.6:c.192+11607C>T

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+11607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 151,968 control chromosomes in the GnomAD database, including 41,809 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 0.73 (41809 hom., cov: 30)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000337.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	NM_000337.6	MANE Select	c.192+11607C>T		intron	N/A	NP_000328.2
	SGCD	NM_001128209.2		c.189+11607C>T		intron	N/A	NP_001121681.1
	SGCD	NM_172244.3		c.192+11607C>T		intron	N/A	NP_758447.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000337851.9	TSL:1 MANE Select	c.192+11607C>T		intron	N/A	ENSP00000338343.4
	SGCD	ENST00000435422.7	TSL:1	c.189+11607C>T		intron	N/A	ENSP00000403003.2
	SGCD	ENST00000959784.1		c.243+6425C>T		intron	N/A	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111114 AN: 151850 Hom.: 41758 Cov.: 30

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.732 AC: 111228 AN: 151968 Hom.: 41809 Cov.: 30 AF XY: 0.738 AC XY: 54792 AN XY: 74264

African (AFR) AF: 0.900 AC: 37352 AN: 41494

American (AMR) AF: 0.690 AC: 10531 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2535 AN: 3466

East Asian (EAS) AF: 0.916 AC: 4695 AN: 5124

South Asian (SAS) AF: 0.843 AC: 4051 AN: 4808

European-Finnish (FIN) AF: 0.634 AC: 6692 AN: 10550

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.631 AC: 42866 AN: 67952

Other (OTH) AF: 0.746 AC: 1576 AN: 2112

Alfa AF: 0.677 Hom.: 9023

Bravo AF: 0.741

Asia WGS AF: 0.869 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.21
PhyloP100		0.11
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: rs1394608; hg19: chr5-155783294;