chr5-156344576-C-G

Position:

• chr5-156344576-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2_Supporting PP3

This summary comes from the ClinGen Evidence Repository: The NM_000337.6: c.91C>G variant in SGCD is a missense variant predicted to cause substitution of arginine by glycine at amino acid 31 (p.Arg31Gly). This variant is absent from gnomAD v2.1.1 and v4.1.0 genomes (note that the variant fails filter in exome data, suggesting it may be a sequencing artifact) (PM2_Supporting). The computational predictor REVEL gives a score of 0.85, which is above the threshold of ≥0.70, evidence that correlates with impact to SGCD function (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): PM2_Supporting, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA200046/MONDO:0015152/186

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGCD NM_000337.6 missense
• Clinical Significance: Uncertain significance reviewed by expert panel B:1
• Conservation: PhyloP100: 1.52

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]

LOC124901120 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: For more information check the summary or visit ClinGen Evidence Repository.
• PP3: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCD	NM_000337.6	c.91C>G	p.Arg31Gly	missense_variant	3/9	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.91C>G	p.Arg31Gly	missense_variant	3/9	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.88C>G	p.Arg30Gly	missense_variant	2/8	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.91C>G	p.Arg31Gly	missense_variant	5/10	5		ENSP00000429378.1
SGCD	ENST00000524347.2	n.91C>G		non_coding_transcript_exon_variant	3/6	5		ENSP00000430794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000473 AC: 69 AN: 1457452 Hom.: 0 Cov.: 32 AF XY: 0.0000607 AC XY: 44 AN XY: 724996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000906

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.0000499

GnomAD4 genome Cov.: 32

ExAC AF: 0.0139 AC: 1679

ClinVar

Significance: Uncertain significance

Submissions summary: Benign:1

Revision: reviewed by expert panel

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.98	.;D;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D;D;D
MetaRNN	Benign	0.016	T;T;T
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.4	D;D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;P;P
Vest4		0.24
MPC		0.65
ClinPred		0.047	T
GERP RS		1.6
Varity_R		0.76
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -28

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202223676; hg19: chr5-155771586; COSMIC: COSV61905583;