rs1394605

Variant names:

• chr5-156332777-G-C
• rs1394605
• NM_000337.6:c.3+3198G>C

Variant summary

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

The NM_000337.6(SGCD):​c.3+3198G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,144 control chromosomes in the GnomAD database, including 817 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 0.091 (817 hom., cov: 32)
• Consequence: SGCD NM_000337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• 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 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.3+3198G>C		intron_variant	Intron 2 of 8	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.3+3198G>C		intron_variant	Intron 2 of 8	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.-1+5545G>C		intron_variant	Intron 1 of 7	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.3+3198G>C		intron_variant	Intron 4 of 9	5		ENSP00000429378.1
SGCD	ENST00000524347.2	n.3+3198G>C		intron_variant	Intron 2 of 5	5		ENSP00000430794.1

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13806 AN: 152024 Hom.: 819 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0925

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

GnomAD4 genome AF: 0.0907 AC: 13797 AN: 152144 Hom.: 817 Cov.: 32 AF XY: 0.0913 AC XY: 6789 AN XY: 74392

African (AFR) AF: 0.0296 AC: 1229 AN: 41534

American (AMR) AF: 0.0849 AC: 1298 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 333 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0847 AC: 408 AN: 4818

European-Finnish (FIN) AF: 0.176 AC: 1865 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8186 AN: 67972

Other (OTH) AF: 0.0919 AC: 194 AN: 2110

Alfa AF: 0.102 Hom.: 122

Bravo AF: 0.0812

Asia WGS AF: 0.0400 AC: 140 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	1.3
DANN	Benign	0.41
PhyloP100		-0.060
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: rs1394605; hg19: chr5-155759787;