rs1800350

Variant names:

• chr13-23234643-T-C
• rs1800350
• NM_000231.3:c.228T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000231.3(SGCG):​c.228T>C​(p.Asp76Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,610,324 control chromosomes in the GnomAD database, including 13,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1990 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11346 hom.)
• Consequence: SGCG NM_000231.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 1.46
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 13-23234643-T-C is Benign according to our data. Variant chr13-23234643-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 92653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	NM_000231.3	MANE Select	c.228T>C	p.Asp76Asp	synonymous	Exon 3 of 8	NP_000222.2
	SGCG	NM_001378244.1		c.282T>C	p.Asp94Asp	synonymous	Exon 3 of 8	NP_001365173.1
	SGCG	NM_001378245.1		c.228T>C	p.Asp76Asp	synonymous	Exon 4 of 9	NP_001365174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCG	ENST00000218867.4	TSL:1 MANE Select	c.228T>C	p.Asp76Asp	synonymous	Exon 3 of 8	ENSP00000218867.3
	SGCG	ENST00000942469.1		c.228T>C	p.Asp76Asp	synonymous	Exon 3 of 9	ENSP00000612528.1
	SGCG	ENST00000876364.1		c.228T>C	p.Asp76Asp	synonymous	Exon 4 of 9	ENSP00000546423.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22276 AN: 151854 Hom.: 1988 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.105 AC: 26294 AN: 251362 AF XY: 0.104

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.0573

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.000815

Gnomad FIN exome AF: 0.0795

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.118 AC: 172428 AN: 1458354 Hom.: 11346 Cov.: 31 AF XY: 0.117 AC XY: 84883 AN XY: 725660

African (AFR) AF: 0.252 AC: 8390 AN: 33350

American (AMR) AF: 0.0614 AC: 2747 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3376 AN: 26104

East Asian (EAS) AF: 0.000429 AC: 17 AN: 39632

South Asian (SAS) AF: 0.101 AC: 8663 AN: 86166

European-Finnish (FIN) AF: 0.0843 AC: 4502 AN: 53412

Middle Eastern (MID) AF: 0.0779 AC: 448 AN: 5752

European-Non Finnish (NFE) AF: 0.124 AC: 137031 AN: 1108950

Other (OTH) AF: 0.120 AC: 7254 AN: 60266

GnomAD4 genome AF: 0.147 AC: 22283 AN: 151970 Hom.: 1990 Cov.: 32 AF XY: 0.141 AC XY: 10438 AN XY: 74288

African (AFR) AF: 0.248 AC: 10289 AN: 41412

American (AMR) AF: 0.102 AC: 1554 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.101 AC: 488 AN: 4820

European-Finnish (FIN) AF: 0.0780 AC: 823 AN: 10552

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8284 AN: 67970

Other (OTH) AF: 0.128 AC: 270 AN: 2102

Alfa AF: 0.134 Hom.: 1270

Bravo AF: 0.154

Asia WGS AF: 0.0640 AC: 224 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.118

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Autosomal recessive limb-girdle muscular dystrophy type 2C (3)
-	-	2	not provided (2)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Sarcoglycanopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.7
DANN	Benign	0.44
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1800350; hg19: chr13-23808782;