Variant 12-64747808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002076.4(GNS):c.363G>A(p.Lys121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,608,308 control chromosomes in the GnomAD database, including 11,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 813 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10997 hom. )

Consequence

GNS
NM_002076.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.135

Variant links:

Genes affected

GNS (HGNC:4422): (glucosamine (N-acetyl)-6-sulfatase) The product of this gene is a lysosomal enzyme found in all cells. It is involved in the catabolism of heparin, heparan sulphate, and keratan sulphate. Deficiency of this enzyme results in the accumulation of undegraded substrate and the lysosomal storage disorder mucopolysaccharidosis type IIID (Sanfilippo D syndrome). Mucopolysaccharidosis type IIID is the least common of the four subtypes of Sanfilippo syndrome. [provided by RefSeq, Jul 2008]

GNS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 12-64747808-C-T is Benign according to our data. Variant chr12-64747808-C-T is described in ClinVar as [Benign]. Clinvar id is 94030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-64747808-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.135 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNS	NM_002076.4 linkuse as main transcript	c.363G>A	p.Lys121=	synonymous_variant	3/14	ENST00000258145.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNS	ENST00000258145.8 linkuse as main transcript	c.363G>A	p.Lys121=	synonymous_variant	3/14	1	NM_002076.4	P1	P15586-1

Frequencies

GnomAD3 genomes

AF:

0.0888

AC:

13512

AN:

152098

Hom.:

814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0785

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.0937

GnomAD3 exomes

AF:

0.0924

AC:

23248

AN:

251476

Hom.:

1451

AF XY:

0.0929

AC XY:

12626

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.0612

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0288

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.115

AC:

168050

AN:

1456092

Hom.:

10997

Cov.:

AF XY:

0.113

AC XY:

82068

AN XY:

724802

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.0660

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0289

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0888

AC:

13514

AN:

152216

Hom.:

813

Cov.:

AF XY:

0.0882

AC XY:

6566

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.0784

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0219

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.0922

Alfa

AF:

0.117

Hom.:

606

Bravo

AF:

0.0826

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.134

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 03, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 09, 2017	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. -

Mucopolysaccharidosis, MPS-III-D

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided

Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 23, 2015

- -

Sanfilippo syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.84

DANN

Benign

0.43

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