5-156728144-C-T

Variant names:

• chr5-156728144-C-T
• rs456290
• NM_000337.6:c.576-29437C>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.576-29437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,986 control chromosomes in the GnomAD database, including 42,429 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 (42429 hom., cov: 31)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 4 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, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ENSG00000254163 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.805 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.576-29437C>T		intron	N/A	NP_000328.2
	SGCD	NM_001128209.2		c.573-29437C>T		intron	N/A	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.576-29437C>T		intron	N/A	NP_758447.1	Q92629-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000337851.9	TSL:1 MANE Select	c.576-29437C>T		intron	N/A	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.573-29437C>T		intron	N/A	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.627-29437C>T		intron	N/A	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111561 AN: 151868 Hom.: 42430 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.734 AC: 111582 AN: 151986 Hom.: 42429 Cov.: 31 AF XY: 0.740 AC XY: 54996 AN XY: 74298

African (AFR) AF: 0.513 AC: 21231 AN: 41392

American (AMR) AF: 0.806 AC: 12327 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3051 AN: 3470

East Asian (EAS) AF: 0.804 AC: 4158 AN: 5172

South Asian (SAS) AF: 0.814 AC: 3913 AN: 4808

European-Finnish (FIN) AF: 0.861 AC: 9118 AN: 10586

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55075 AN: 67962

Other (OTH) AF: 0.778 AC: 1639 AN: 2108

Alfa AF: 0.792 Hom.: 26800

Bravo AF: 0.719

Asia WGS AF: 0.773 AC: 2686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		0.27
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: rs456290; hg19: chr5-156155155;