rs1801190

Variant names:

• chr17-50168516-C-T
• rs1801190
• NM_000023.4:c.528C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000023.4(SGCA):​c.528C>T​(p.Thr176Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,580,106 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (28 hom.)
• Consequence: SGCA NM_000023.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.242

Genes affected

SGCA (HGNC:10805): (sarcoglycan alpha) This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 17-50168516-C-T is Benign according to our data. Variant chr17-50168516-C-T is described in ClinVar as [Benign]. Clinvar id is 130293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50168516-C-T is described in Lovd as [Benign]. Variant chr17-50168516-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.242 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00863 (1314/152270) while in subpopulation AFR AF= 0.028 (1163/41550). AF 95% confidence interval is 0.0267. There are 17 homozygotes in gnomad4. There are 653 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCA	NM_000023.4	c.528C>T	p.Thr176Thr	synonymous_variant	Exon 5 of 10	ENST00000262018.8	NP_000014.1
SGCA	NM_001135697.3	c.528C>T	p.Thr176Thr	synonymous_variant	Exon 5 of 8		NP_001129169.1
SGCA	NR_135553.2	n.564C>T		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCA	ENST00000262018.8	c.528C>T	p.Thr176Thr	synonymous_variant	Exon 5 of 10	1	NM_000023.4	ENSP00000262018.3

Frequencies

GnomAD3 genomes AF: 0.00855 AC: 1301 AN: 152152 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00926

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00277 AC: 541 AN: 194982 Hom.: 3 AF XY: 0.00218 AC XY: 227 AN XY: 104318

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00669

Gnomad SAS exome AF: 0.000278

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00219

GnomAD4 exome AF: 0.00134 AC: 1909 AN: 1427836 Hom.: 28 Cov.: 33 AF XY: 0.00124 AC XY: 875 AN XY: 706898

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.00211

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00785

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000251

Gnomad4 OTH exome AF: 0.00365

GnomAD4 genome AF: 0.00863 AC: 1314 AN: 152270 Hom.: 17 Cov.: 32 AF XY: 0.00877 AC XY: 653 AN XY: 74458

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00909

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00402 Hom.: 1

Bravo AF: 0.00941

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jan 10, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive limb-girdle muscular dystrophy type 2D Benign:3

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Sep 21, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sarcoglycanopathy Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.3
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801190; hg19: chr17-48245877;