NM_000231.3:c.505+46T>A

Variant names:

• chr13-23279524-T-A
• rs17078558
• NM_000231.3:c.505+46T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000231.3(SGCG):​c.505+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,590,500 control chromosomes in the GnomAD database, including 777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (64 hom., cov: 32)
  • Exomes 𝑓: 0.026 (713 hom.)
• Consequence: SGCG NM_000231.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.498
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-23279524-T-A is Benign according to our data. Variant chr13-23279524-T-A is described in ClinVar as Benign. ClinVar VariationId is 255602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0735 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.505+46T>A		intron	N/A	NP_000222.2	Q13326
	SGCG	NM_001378244.1		c.559+46T>A		intron	N/A	NP_001365173.1
	SGCG	NM_001378245.1		c.505+46T>A		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.505+46T>A		intron	N/A	ENSP00000218867.3	Q13326
	SGCG	ENST00000942469.1		c.505+46T>A		intron	N/A	ENSP00000612528.1
	SGCG	ENST00000876364.1		c.505+46T>A		intron	N/A	ENSP00000546423.1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3313 AN: 152006 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0320 AC: 7865 AN: 245708 AF XY: 0.0320

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.0437

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.0721

Gnomad FIN exome AF: 0.0479

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0224

GnomAD4 exome AF: 0.0261 AC: 37513 AN: 1438376 Hom.: 713 Cov.: 26 AF XY: 0.0265 AC XY: 18992 AN XY: 716194

African (AFR) AF: 0.00298 AC: 98 AN: 32896

American (AMR) AF: 0.0414 AC: 1829 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.00884 AC: 227 AN: 25678

East Asian (EAS) AF: 0.0914 AC: 3563 AN: 38992

South Asian (SAS) AF: 0.0448 AC: 3804 AN: 84880

European-Finnish (FIN) AF: 0.0476 AC: 2484 AN: 52204

Middle Eastern (MID) AF: 0.00738 AC: 42 AN: 5694

European-Non Finnish (NFE) AF: 0.0218 AC: 23907 AN: 1094534

Other (OTH) AF: 0.0263 AC: 1559 AN: 59322

GnomAD4 genome AF: 0.0218 AC: 3313 AN: 152124 Hom.: 64 Cov.: 32 AF XY: 0.0229 AC XY: 1705 AN XY: 74368

African (AFR) AF: 0.00390 AC: 162 AN: 41510

American (AMR) AF: 0.0268 AC: 410 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.0798 AC: 412 AN: 5160

South Asian (SAS) AF: 0.0462 AC: 222 AN: 4810

European-Finnish (FIN) AF: 0.0470 AC: 498 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0226 AC: 1534 AN: 67986

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0228 Hom.: 9

Bravo AF: 0.0199

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.76
PhyloP100		-0.50
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: rs17078558; hg19: chr13-23853663;