rs112672390

Variant names:

• chr13-23203521-A-C
• rs112672390
• NM_000231.3:c.1-174A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-23203521-A-C
• chr13-23203521-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000231.3(SGCG):​c.1-174A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 152,374 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0033 (2 hom., cov: 33)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510
• Publications: 0 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, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2C

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 13-23203521-A-C is Benign according to our data. Variant chr13-23203521-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1188460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00333 (508/152374) while in subpopulation AFR AF = 0.0115 (479/41584). AF 95% confidence interval is 0.0107. There are 2 homozygotes in GnomAd4. There are 248 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	NM_000231.3	MANE Select	c.1-174A>C		intron	N/A	NP_000222.2	Q13326
	SGCG	NM_001378244.1		c.55-174A>C		intron	N/A	NP_001365173.1
	SGCG	NM_001378245.1		c.1-174A>C		intron	N/A	NP_001365174.1	Q13326

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	ENST00000218867.4	TSL:1 MANE Select	c.1-174A>C		intron	N/A	ENSP00000218867.3	Q13326
	SGCG	ENST00000942469.1		c.1-174A>C		intron	N/A	ENSP00000612528.1
	SGCG	ENST00000876364.1		c.1-174A>C		intron	N/A	ENSP00000546423.1

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 505 AN: 152256 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

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

GnomAD4 genome AF: 0.00333 AC: 508 AN: 152374 Hom.: 2 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74518

African (AFR) AF: 0.0115 AC: 479 AN: 41584

American (AMR) AF: 0.00150 AC: 23 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00391

Asia WGS AF: 0.00116 AC: 4 AN: 3472

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.1
DANN	Benign	0.77
PhyloP100		-0.051

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: rs112672390; hg19: chr13-23777660;