Variant 13-23180988-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001378245.1(SGCG):c.-152+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,152 control chromosomes in the GnomAD database, including 1,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1846 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

SGCG
NM_001378245.1 splice_region, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.306

Variant links:

Genes affected

SGCG (HGNC:10809): (sarcoglycan gamma) This gene encodes gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C). [provided by RefSeq, Oct 2008]

SGCG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 13-23180988-G-A is Benign according to our data. Variant chr13-23180988-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 311478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-23180988-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCG	NM_000231.3 link	c.-88G>A		5_prime_UTR_variant	1/8	ENST00000218867.4	NP_000222.2	Q13326

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCG	ENST00000218867 link	c.-88G>A		5_prime_UTR_variant	1/8	1	NM_000231.3	ENSP00000218867.3		Q13326

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22881

AN:

152030

Hom.:

1838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.500

GnomAD4 genome

AF:

0.151

AC:

22905

AN:

152148

Hom.:

1846

Cov.:

AF XY:

0.147

AC XY:

10907

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.180

Hom.:

3833

Bravo

AF:

0.148

Asia WGS

AF:

0.141

AC:

490

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 19, 2019	- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Sarcoglycanopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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