13-23203603-C-T

Variant names:

• chr13-23203603-C-T
• rs114229961
• NM_000231.3:c.1-92C>T

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.1-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 863,784 control chromosomes in the GnomAD database, including 3 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)
  • Exomes 𝑓: 0.00044 (1 hom.)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.136
• 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=-0.85).
• BP6: Variant 13-23203603-C-T is Benign according to our data. Variant chr13-23203603-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1201163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00332 (506/152226) while in subpopulation AFR AF = 0.0115 (477/41548). AF 95% confidence interval is 0.0106. 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.1-92C>T		intron	N/A	NP_000222.2	Q13326
	SGCG	NM_001378244.1		c.55-92C>T		intron	N/A	NP_001365173.1
	SGCG	NM_001378245.1		c.1-92C>T		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.1-92C>T		intron	N/A	ENSP00000218867.3	Q13326
	SGCG	ENST00000942469.1		c.1-92C>T		intron	N/A	ENSP00000612528.1
	SGCG	ENST00000876364.1		c.1-92C>T		intron	N/A	ENSP00000546423.1

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 503 AN: 152108 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

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: 0.00144

GnomAD4 exome AF: 0.000444 AC: 316 AN: 711558 Hom.: 1 AF XY: 0.000352 AC XY: 132 AN XY: 375098

African (AFR) AF: 0.0115 AC: 212 AN: 18496

American (AMR) AF: 0.00124 AC: 43 AN: 34720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20848

East Asian (EAS) AF: 0.00 AC: 0 AN: 32648

South Asian (SAS) AF: 0.0000154 AC: 1 AN: 64902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48072

Middle Eastern (MID) AF: 0.000281 AC: 1 AN: 3560

European-Non Finnish (NFE) AF: 0.0000221 AC: 10 AN: 452856

Other (OTH) AF: 0.00138 AC: 49 AN: 35456

GnomAD4 genome AF: 0.00332 AC: 506 AN: 152226 Hom.: 2 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74424

African (AFR) AF: 0.0115 AC: 477 AN: 41548

American (AMR) AF: 0.00150 AC: 23 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67998

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00390

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	-0.85
CADD	Benign	0.70
DANN	Benign	0.70
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

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: rs114229961; hg19: chr13-23777742;