rs3794370

Variant names:

• chr13-23182488-T-G
• rs3794370
• NM_000231.3:c.-1+1413T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

SGCG Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2C

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGCG	NM_000231.3	c.-1+1413T>G		intron_variant	Intron 1 of 7	ENST00000218867.4	NP_000222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCG	ENST00000218867.4	c.-1+1413T>G		intron_variant	Intron 1 of 7	1	NM_000231.3	ENSP00000218867.3

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

African (AFR) AF: 0.385 AC: 15591 AN: 40496

American (AMR) AF: 0.590 AC: 8919 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1642 AN: 3420

East Asian (EAS) AF: 0.598 AC: 2974 AN: 4972

South Asian (SAS) AF: 0.551 AC: 2545 AN: 4618

European-Finnish (FIN) AF: 0.600 AC: 6109 AN: 10190

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 33978 AN: 67240

Other (OTH) AF: 0.511 AC: 1067 AN: 2090

Alfa AF: 0.495 Hom.: 32068

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
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3794370; hg19: chr13-23756627;