20-34945933-A-C

Position:

chr20-34945933-A-C

Variant summary

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

The NM_000178.4(GSS):c.275+20T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,611,838 control chromosomes in the GnomAD database, including 323,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36631 hom., cov: 33)

Exomes 𝑓: 0.62 ( 286520 hom. )

Consequence

GSS
NM_000178.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.60

Variant links:

Genes affected

GSS (HGNC:4624): (glutathione synthetase) Glutathione is important for a variety of biological functions, including protection of cells from oxidative damage by free radicals, detoxification of xenobiotics, and membrane transport. The protein encoded by this gene functions as a homodimer to catalyze the second step of glutathione biosynthesis, which is the ATP-dependent conversion of gamma-L-glutamyl-L-cysteine to glutathione. Defects in this gene are a cause of glutathione synthetase deficiency. [provided by RefSeq, Jul 2008]

GSS 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 20-34945933-A-C is Benign according to our data. Variant chr20-34945933-A-C is described in ClinVar as [Benign]. Clinvar id is 255474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-34945933-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
GSS	NM_000178.4 linkuse as main transcript	c.275+20T>G	intron_variant	ENST00000651619.1	NP_000169.1
GSS	NM_001322494.1 linkuse as main transcript	c.275+20T>G	intron_variant		NP_001309423.1
GSS	NM_001322495.1 linkuse as main transcript	c.275+20T>G	intron_variant		NP_001309424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1 linkuse as main transcript	c.275+20T>G		intron_variant			NM_000178.4	ENSP00000498303	P1	P48637-1

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102712

AN:

151970

Hom.:

36571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.627

GnomAD3 exomes

AF:

0.600

AC:

150741

AN:

251084

Hom.:

48354

AF XY:

0.612

AC XY:

83016

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.919

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.636

Gnomad EAS exome

AF:

0.484

Gnomad SAS exome

AF:

0.744

Gnomad FIN exome

AF:

0.608

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.621

AC:

905987

AN:

1459750

Hom.:

286520

Cov.:

AF XY:

0.624

AC XY:

453408

AN XY:

726278

show subpopulations

Gnomad4 AFR exome

AF:

0.921

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.637

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.604

Gnomad4 NFE exome

AF:

0.620

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.676

AC:

102813

AN:

152088

Hom.:

36631

Cov.:

AF XY:

0.672

AC XY:

49971

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.906

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.629

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.738

Gnomad4 FIN

AF:

0.596

Gnomad4 NFE

AF:

0.613

Gnomad4 OTH

AF:

0.631

Alfa

AF:

0.619

Hom.:

7758

Bravo

AF:

0.668

Asia WGS

AF:

0.624

AC:

2173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jan 23, 2017	Variant summary: The GSS c.275+20T>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. This variant was found in 75115/121240 control chromosomes (24686 homozygotes) in ExAC at a frequency of 0.6195563, and is present in as much as 91% in sub-populations (Africa), therefore indicating this variant is the major allele and is a benign polymorphism. In addition, at least one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Glutathione synthetase deficiency without 5-oxoprolinuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Glutathione synthetase deficiency with 5-oxoprolinuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Inherited glutathione synthetase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.3

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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