rs59944537

chr17-50167908-C-Achr17-50167908-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000023.4(SGCA):c.313-39C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,601,502 control chromosomes in the GnomAD database, including 16,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1663 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15177 hom.)
• Consequence: SGCA NM_000023.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.334

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-50167908-C-A is Benign according to our data. Variant chr17-50167908-C-A is described in ClinVar as [Benign]. Clinvar id is 254718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50167908-C-A is described in Lovd as [Benign]. Variant chr17-50167908-C-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCA	NM_000023.4	c.313-39C>A		intron_variant		ENST00000262018.8
SGCA	NM_001135697.3	c.313-39C>A		intron_variant
SGCA	NR_135553.2	n.349-39C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCA	ENST00000262018.8	c.313-39C>A		intron_variant		1	NM_000023.4	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22322 AN: 152112 Hom.: 1664 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.145 AC: 36560 AN: 251446 Hom.: 2987 AF XY: 0.143 AC XY: 19371 AN XY: 135904

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.0378

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.142 AC: 205274 AN: 1449272 Hom.: 15177 Cov.: 31 AF XY: 0.142 AC XY: 102230 AN XY: 721692

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0452

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.147 AC: 22339 AN: 152230 Hom.: 1663 Cov.: 32 AF XY: 0.147 AC XY: 10979 AN XY: 74434

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0444

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.127

Alfa AF: 0.147 Hom.: 324

Bravo AF: 0.149

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Autosomal recessive limb-girdle muscular dystrophy type 2D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.3
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs59944537; hg19: chr17-48245269; COSMIC: COSV56249545; COSMIC: COSV56249545;