rs59944537

Variant names:

• chr17-50167908-C-A
• rs59944537
• NM_000023.4:c.313-39C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50167908-C-A
• chr17-50167908-C-G
• chr17-50167908-C-T

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.334
• Publications: 3 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 -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 VariationId is 254718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
SGCA	NM_000023.4	c.313-39C>A		intron_variant	Intron 3 of 9	ENST00000262018.8	NP_000014.1
SGCA	NM_001135697.3	c.313-39C>A		intron_variant	Intron 3 of 7		NP_001129169.1
SGCA	NR_135553.2	n.349-39C>A		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCA	ENST00000262018.8	c.313-39C>A		intron_variant	Intron 3 of 9	1	NM_000023.4	ENSP00000262018.3

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

GnomAD2 exomes AF: 0.145 AC: 36560 AN: 251446 AF XY: 0.143

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 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

African (AFR) AF: 0.158 AC: 5243 AN: 33238

American (AMR) AF: 0.211 AC: 9451 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3217 AN: 26054

East Asian (EAS) AF: 0.0452 AC: 1792 AN: 39642

South Asian (SAS) AF: 0.130 AC: 11163 AN: 85996

European-Finnish (FIN) AF: 0.153 AC: 8180 AN: 53384

Middle Eastern (MID) AF: 0.143 AC: 824 AN: 5744

European-Non Finnish (NFE) AF: 0.143 AC: 157211 AN: 1100558

Other (OTH) AF: 0.137 AC: 8193 AN: 59950

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

African (AFR) AF: 0.152 AC: 6323 AN: 41516

American (AMR) AF: 0.184 AC: 2819 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3472

East Asian (EAS) AF: 0.0444 AC: 230 AN: 5180

South Asian (SAS) AF: 0.136 AC: 656 AN: 4830

European-Finnish (FIN) AF: 0.145 AC: 1541 AN: 10616

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9886 AN: 68000

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.147 Hom.: 332

Bravo AF: 0.149

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.69
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs59944537; hg19: chr17-48245269; COSMIC: COSV56249545; COSMIC: COSV56249545;