rs59944537

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.334

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
SGCA	NM_000023.4 link	c.313-39C>A	intron_variant	Intron 3 of 9	ENST00000262018.8	NP_000014.1	Q16586-1A0A0S2Z4Q1
SGCA	NM_001135697.3 link	c.313-39C>A	intron_variant	Intron 3 of 7		NP_001129169.1	Q16586-2A0A0S2Z4P8
SGCA	NR_135553.2 link	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 link	c.313-39C>A		intron_variant	Intron 3 of 9	1	NM_000023.4	ENSP00000262018.3		Q16586-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22322

AN:

152112

Hom.:

1664

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.142

AC XY:

102230

AN XY:

721692

show subpopulations

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.:

AF XY:

0.147

AC XY:

10979

AN XY:

74434

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over