rs66844808

Positions:

• chr13-23279329-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000231.3(SGCG):​c.386-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,603,962 control chromosomes in the GnomAD database, including 11,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (975 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10505 hom.)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.123

Genes affected

SGCG (HGNC:10809): (sarcoglycan gamma) This gene encodes gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-23279329-A-G is Benign according to our data. Variant chr13-23279329-A-G is described in ClinVar as [Benign]. Clinvar id is 255601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-23279329-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCG	NM_000231.3	c.386-30A>G		intron_variant		ENST00000218867.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCG	ENST00000218867.4	c.386-30A>G		intron_variant		1	NM_000231.3	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16047 AN: 152024 Hom.: 973 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.0962 AC: 24134 AN: 250788 Hom.: 1415 AF XY: 0.0967 AC XY: 13112 AN XY: 135586

Gnomad AFR exome AF: 0.0808

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0410

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.115 AC: 166690 AN: 1451820 Hom.: 10505 Cov.: 30 AF XY: 0.113 AC XY: 81649 AN XY: 722494

Gnomad4 AFR exome AF: 0.0798

Gnomad4 AMR exome AF: 0.0804

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.000431

Gnomad4 SAS exome AF: 0.0431

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.106 AC: 16059 AN: 152142 Hom.: 975 Cov.: 32 AF XY: 0.104 AC XY: 7760 AN XY: 74384

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.119

Alfa AF: 0.119 Hom.: 199

Bravo AF: 0.104

Asia WGS AF: 0.0280 AC: 100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Autosomal recessive limb-girdle muscular dystrophy type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs66844808; hg19: chr13-23853468;