13-23320615-G-T

Position:

chr13-23320615-G-T

Variant summary

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

The NM_000231.3(SGCG):c.579-22G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 12 hom., cov: 0)

Exomes 𝑓: 0.063 ( 1291 hom. )

Failed GnomAD Quality Control

Consequence

SGCG
NM_000231.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.375

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:

SACS (HGNC:10519): (sacsin molecular chaperone) This gene encodes the sacsin protein, which includes a UbL domain at the N-terminus, a DnaJ domain, and a HEPN domain at the C-terminus. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. This gene includes a very large exon spanning more than 12.8 kb. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. The authors of a publication on the effects of siRNA-mediated sacsin knockdown concluded that sacsin protects against mutant ataxin-1 and suggest that "the large multi-domain sacsin protein is able to recruit Hsp70 chaperone action and has the potential to regulate the effects of other ataxia proteins" (Parfitt et al., PubMed: 19208651). A pseudogene associated with this gene is located on chromosome 11. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

SACS links:

LOC107984585 (HGNC:):

LOC107984585 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=-0.91).

BP6

Variant 13-23320615-G-T is Benign according to our data. Variant chr13-23320615-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 255603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-23320615-G-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCG	NM_000231.3 link	c.579-22G>T		intron_variant		ENST00000218867.4	NP_000222.2	Q13326

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SGCG	ENST00000218867.4 link	c.579-22G>T	intron_variant	1	NM_000231.3	ENSP00000218867.3	Q13326
SACS	ENST00000682775.1 link	c.2186-8500C>A	intron_variant			ENSP00000508399.1	A0A804HLK7
SACS	ENST00000683210.1 link	c.2186-31372C>A	intron_variant			ENSP00000506739.1	A0A804HHS6
SACS	ENST00000684325.1 link	n.*104+951C>A	intron_variant			ENSP00000508121.1	A0A804HKY6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1041

AN:

47416

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.00463

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0136

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.0119

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0131

GnomAD3 exomes

AF:

0.136

AC:

13558

AN:

99330

Hom.:

1133

AF XY:

0.143

AC XY:

7622

AN XY:

53176

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.0889

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.0754

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0628

AC:

40498

AN:

645318

Hom.:

1291

Cov.:

AF XY:

0.0642

AC XY:

20422

AN XY:

318308

show subpopulations

Gnomad4 AFR exome

AF:

0.0421

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.0685

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.0538

Gnomad4 OTH exome

AF:

0.0628

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0221

AC:

1048

AN:

47470

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

542

AN XY:

23386

show subpopulations

Gnomad4 AFR

AF:

0.0274

Gnomad4 AMR

AF:

0.0187

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.0143

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.0253

Gnomad4 NFE

AF:

0.0209

Gnomad4 OTH

AF:

0.0160

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.79

DANN

Benign

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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