13-23279408-C-T

Variant names:

• chr13-23279408-C-T
• rs35628352
• NM_000231.3:c.435C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000231.3(SGCG):​c.435C>T​(p.Asn145Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,613,022 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (25 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (14 hom.)
• Consequence: SGCG NM_000231.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0630
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 13-23279408-C-T is Benign according to our data. Variant chr13-23279408-C-T is described in ClinVar as Benign. ClinVar VariationId is 130295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.063 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00894 (1360/152178) while in subpopulation AFR AF = 0.0305 (1264/41500). AF 95% confidence interval is 0.0291. There are 25 homozygotes in GnomAd4. There are 648 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 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.435C>T	p.Asn145Asn	synonymous	Exon 5 of 8	NP_000222.2	Q13326
	SGCG	NM_001378244.1		c.489C>T	p.Asn163Asn	synonymous	Exon 5 of 8	NP_001365173.1
	SGCG	NM_001378245.1		c.435C>T	p.Asn145Asn	synonymous	Exon 6 of 9	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.435C>T	p.Asn145Asn	synonymous	Exon 5 of 8	ENSP00000218867.3	Q13326
	SGCG	ENST00000942469.1		c.435C>T	p.Asn145Asn	synonymous	Exon 5 of 9	ENSP00000612528.1
	SGCG	ENST00000876364.1		c.435C>T	p.Asn145Asn	synonymous	Exon 6 of 9	ENSP00000546423.1

Frequencies

GnomAD3 genomes AF: 0.00890 AC: 1354 AN: 152060 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00464

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: 0.000191

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00228 AC: 572 AN: 251284 AF XY: 0.00158

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000913 AC: 1334 AN: 1460844 Hom.: 14 Cov.: 31 AF XY: 0.000813 AC XY: 591 AN XY: 726744

African (AFR) AF: 0.0322 AC: 1077 AN: 33450

American (AMR) AF: 0.00157 AC: 70 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111236

Other (OTH) AF: 0.00219 AC: 132 AN: 60344

GnomAD4 genome AF: 0.00894 AC: 1360 AN: 152178 Hom.: 25 Cov.: 32 AF XY: 0.00871 AC XY: 648 AN XY: 74382

African (AFR) AF: 0.0305 AC: 1264 AN: 41500

American (AMR) AF: 0.00464 AC: 71 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00481 Hom.: 5

Bravo AF: 0.0102

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2C (2)
-	-	1	not provided (1)
-	-	1	Sarcoglycanopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		0.063
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: rs35628352; hg19: chr13-23853547;