rs79410682

Variant names:

• chr17-50166100-G-A
• rs79410682
• NM_000023.4:c.37+23G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4 BA1 BP7

This summary comes from the ClinGen Evidence Repository: The NM_000023.4: c.37+23G>A variant in SGCA is located in intron 1 of 9. The filtering allele frequency of this variant in SGCA is 0.06791 (the lower threshold of the 95% CI of 1625/21638 exome chromosomes) in the European (non-Finnish) population in gnomAD v2.1.1, which is higher than the ClinGen LGMD VCEP threshold (>0.002) for BA1 and therefore meets this criterion (BA1). This variant is not located in a splice region and is not predicted to impact splicing by SpliceAI (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/07/2025): BA1, BP4, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8643656/MONDO:0015152/189

• Frequency:
  • Genomes: 𝑓 0.046 (228 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2879 hom.)
• Consequence: SGCA NM_000023.4 intron
• Clinical Significance: Benign reviewed by expert panel B:7
• Conservation: PhyloP100: 0.174

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]

LOC105371818 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BP7: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCA	NM_000023.4	c.37+23G>A		intron_variant	Intron 1 of 9	ENST00000262018.8	NP_000014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCA	ENST00000262018.8	c.37+23G>A		intron_variant	Intron 1 of 9	1	NM_000023.4	ENSP00000262018.3

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7081 AN: 152174 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.00996

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0608

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0534 AC: 13275 AN: 248714 Hom.: 454 AF XY: 0.0557 AC XY: 7503 AN XY: 134648

Gnomad AFR exome AF: 0.00878

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.0538

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0580

Gnomad FIN exome AF: 0.0751

Gnomad NFE exome AF: 0.0692

Gnomad OTH exome AF: 0.0566

GnomAD4 exome AF: 0.0597 AC: 86578 AN: 1449886 Hom.: 2879 Cov.: 28 AF XY: 0.0605 AC XY: 43679 AN XY: 722130

Gnomad4 AFR exome AF: 0.00760

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.0526

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0555

Gnomad4 FIN exome AF: 0.0744

Gnomad4 NFE exome AF: 0.0645

Gnomad4 OTH exome AF: 0.0550

GnomAD4 genome AF: 0.0465 AC: 7076 AN: 152292 Hom.: 228 Cov.: 32 AF XY: 0.0467 AC XY: 3480 AN XY: 74460

Gnomad4 AFR AF: 0.00993

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0607

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0596 Hom.: 68

Bravo AF: 0.0414

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: reviewed by expert panel

Submissions by phenotype

not provided Benign:3

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32875335) -

Aug 11, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy Benign:1

Jan 07, 2025

ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The NM_000023.4: c.37+23G>A variant in SGCA is located in intron 1 of 9. The filtering allele frequency of this variant in SGCA is 0.06791 (the lower threshold of the 95% CI of 1625/21638 exome chromosomes) in the European (non-Finnish) population in gnomAD v2.1.1, which is higher than the ClinGen LGMD VCEP threshold (>0.002) for BA1 and therefore meets this criterion (BA1). This variant is not located in a splice region and is not predicted to impact splicing by SpliceAI (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/07/2025): BA1, BP4, BP7. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs79410682; hg19: chr17-48243461;