rs79410682

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

SGCA 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 2D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, Orphanet

ENSG00000253730 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000023.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	NM_000023.4	MANE Select	c.37+23G>A		intron	N/A	NP_000014.1
	SGCA	NM_001135697.3		c.37+23G>A		intron	N/A	NP_001129169.1
	SGCA	NR_135553.2		n.73+23G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	ENST00000262018.8	TSL:1 MANE Select	c.37+23G>A		intron	N/A	ENSP00000262018.3
	SGCA	ENST00000344627.10	TSL:1	c.37+23G>A		intron	N/A	ENSP00000345522.6
	SGCA	ENST00000514934.1	TSL:4	n.60G>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000423168.1

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

GnomAD2 exomes AF: 0.0534 AC: 13275 AN: 248714 AF XY: 0.0557

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 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

African (AFR) AF: 0.00760 AC: 253 AN: 33298

American (AMR) AF: 0.0338 AC: 1509 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0526 AC: 1370 AN: 26050

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39648

South Asian (SAS) AF: 0.0555 AC: 4773 AN: 85994

European-Finnish (FIN) AF: 0.0744 AC: 3976 AN: 53410

Middle Eastern (MID) AF: 0.0719 AC: 412 AN: 5730

European-Non Finnish (NFE) AF: 0.0645 AC: 70972 AN: 1101122

Other (OTH) AF: 0.0550 AC: 3299 AN: 59950

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

African (AFR) AF: 0.00993 AC: 413 AN: 41572

American (AMR) AF: 0.0373 AC: 571 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5172

South Asian (SAS) AF: 0.0607 AC: 293 AN: 4830

European-Finnish (FIN) AF: 0.0736 AC: 781 AN: 10618

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4610 AN: 68002

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0596 Hom.: 68

Bravo AF: 0.0414

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2D (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.71
PhyloP100		0.17
PromoterAI		-0.090	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79410682; hg19: chr17-48243461;