rs3794370

Positions:

• chr13-23182488-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000231.3(SGCG):​c.-1+1413T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 149,326 control chromosomes in the GnomAD database, including 18,276 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 0.49 (18276 hom., cov: 30)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCG	NM_000231.3	c.-1+1413T>G		intron_variant		ENST00000218867.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCG	ENST00000218867.4	c.-1+1413T>G		intron_variant		1	NM_000231.3	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 73331 AN: 149216 Hom.: 18275 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.491 AC: 73356 AN: 149326 Hom.: 18276 Cov.: 30 AF XY: 0.500 AC XY: 36441 AN XY: 72930

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.511

Alfa AF: 0.498 Hom.: 25700

Bravo AF: 0.481

Asia WGS AF: 0.511 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.98
DANN	Benign	0.34

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: rs3794370; hg19: chr13-23756627;