NM_000231.3:c.-1+3023A>G

Variant names:

• chr13-23184098-A-G
• rs512444
• NM_000231.3:c.-1+3023A>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+3023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,134 control chromosomes in the GnomAD database, including 40,370 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 0.73 (40370 hom., cov: 33)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000231.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	NM_000231.3	MANE Select	c.-1+3023A>G		intron	N/A	NP_000222.2
	SGCG	NM_001378244.1		c.55-19597A>G		intron	N/A	NP_001365173.1
	SGCG	NM_001378245.1		c.-152+3115A>G		intron	N/A	NP_001365174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	ENST00000218867.4	TSL:1 MANE Select	c.-1+3023A>G		intron	N/A	ENSP00000218867.3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110370 AN: 152016 Hom.: 40331 Cov.: 33

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.726 AC: 110467 AN: 152134 Hom.: 40370 Cov.: 33 AF XY: 0.723 AC XY: 53763 AN XY: 74378

African (AFR) AF: 0.775 AC: 32161 AN: 41500

American (AMR) AF: 0.646 AC: 9872 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2335 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4829 AN: 5174

South Asian (SAS) AF: 0.757 AC: 3650 AN: 4820

European-Finnish (FIN) AF: 0.668 AC: 7063 AN: 10572

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48242 AN: 68002

Other (OTH) AF: 0.705 AC: 1487 AN: 2108

Alfa AF: 0.713 Hom.: 165104

Bravo AF: 0.726

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.72
PhyloP100		0.18
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: rs512444; hg19: chr13-23758237;