5-156344629-G-A

Variant names:

• chr5-156344629-G-A
• rs372152495
• NM_000337.6:c.144G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000337.6(SGCD):​c.144G>A​(p.Val48Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000685 in 1,459,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V48V) has been classified as Likely benign. The gene SGCD is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SGCD NM_000337.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08
• Publications: 0 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

LOC124901120 (HGNC:):

ACMG classification

Specifications for SGCD are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

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.144G>A	p.Val48Val	synonymous	Exon 3 of 9	NP_000328.2
	SGCD	NM_001128209.2		c.141G>A	p.Val47Val	synonymous	Exon 2 of 8	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.144G>A	p.Val48Val	synonymous	Exon 3 of 8	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.144G>A	p.Val48Val	synonymous	Exon 3 of 9	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.141G>A	p.Val47Val	synonymous	Exon 2 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.144G>A	p.Val48Val	synonymous	Exon 3 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459652 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726036

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110966

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.5
DANN	Benign	0.84
PhyloP100		5.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372152495; hg19: chr5-155771639;