rs157350

Variant names:

• chr5-156712558-G-A
• rs157350
• NM_000337.6:c.576-45023G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-156712558-G-A
• chr5-156712558-G-C
• chr5-156712558-G-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.576-45023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,310 control chromosomes in the GnomAD database, including 64,387 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 0.92 (64387 hom., cov: 33)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 16 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

ENSG00000254163 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.576-45023G>A		intron_variant	Intron 7 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.576-45023G>A		intron_variant	Intron 7 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.573-45023G>A		intron_variant	Intron 6 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.576-45023G>A		intron_variant	Intron 9 of 9	5		ENSP00000429378.1
ENSG00000254163	ENST00000520705.1	n.243-8283C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139739 AN: 152192 Hom.: 64324 Cov.: 33

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.918 AC: 139861 AN: 152310 Hom.: 64387 Cov.: 33 AF XY: 0.922 AC XY: 68650 AN XY: 74472

African (AFR) AF: 0.974 AC: 40489 AN: 41572

American (AMR) AF: 0.933 AC: 14269 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5117 AN: 5190

South Asian (SAS) AF: 0.910 AC: 4394 AN: 4830

European-Finnish (FIN) AF: 0.920 AC: 9771 AN: 10616

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59589 AN: 68010

Other (OTH) AF: 0.910 AC: 1924 AN: 2114

Alfa AF: 0.890 Hom.: 132470

Bravo AF: 0.921

Asia WGS AF: 0.929 AC: 3231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.77
PhyloP100		-0.41
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: rs157350; hg19: chr5-156139569;