rs17078558

chr13-23279524-T-A

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.505+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,590,500 control chromosomes in the GnomAD database, including 777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (64 hom., cov: 32)
  • Exomes 𝑓: 0.026 (713 hom.)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.498

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=-0.86).
• BP6: Variant 13-23279524-T-A is Benign according to our data. Variant chr13-23279524-T-A is described in ClinVar as [Benign]. Clinvar id is 255602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-23279524-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCG	NM_000231.3	c.505+46T>A		intron_variant		ENST00000218867.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCG	ENST00000218867.4	c.505+46T>A		intron_variant		1	NM_000231.3	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3313 AN: 152006 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.0320 AC: 7865 AN: 245708 Hom.: 180 AF XY: 0.0320 AC XY: 4245 AN XY: 132822

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.0437

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.0721

Gnomad SAS exome AF: 0.0456

Gnomad FIN exome AF: 0.0479

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0224

GnomAD4 exome AF: 0.0261 AC: 37513 AN: 1438376 Hom.: 713 Cov.: 26 AF XY: 0.0265 AC XY: 18992 AN XY: 716194

Gnomad4 AFR exome AF: 0.00298

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.00884

Gnomad4 EAS exome AF: 0.0914

Gnomad4 SAS exome AF: 0.0448

Gnomad4 FIN exome AF: 0.0476

Gnomad4 NFE exome AF: 0.0218

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0218 AC: 3313 AN: 152124 Hom.: 64 Cov.: 32 AF XY: 0.0229 AC XY: 1705 AN XY: 74368

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0470

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0228 Hom.: 9

Bravo AF: 0.0199

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.7
Dann	Benign	0.76

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: rs17078558; hg19: chr13-23853663;