Variant 20-34929211-A-G 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_000178.4(GSS):c.1301+190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 698,280 control chromosomes in the GnomAD database, including 140,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 35085 hom., cov: 31)

Exomes 𝑓: 0.61 ( 105723 hom. )

Consequence

GSS
NM_000178.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.588

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:

GSS (HGNC:):

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 (MetaRNN=7.439554E-4).

BP6

Variant 20-34929211-A-G is Benign according to our data. Variant chr20-34929211-A-G is described in ClinVar as [Benign]. Clinvar id is 1232487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GSS	NM_000178.4 linkuse as main transcript	c.1301+190T>C	intron_variant	ENST00000651619.1	NP_000169.1	P48637-1V9HWJ1
GSS	NM_001322494.1 linkuse as main transcript	c.1301+190T>C	intron_variant		NP_001309423.1	P48637-1V9HWJ1
GSS	NM_001322495.1 linkuse as main transcript	c.1301+190T>C	intron_variant		NP_001309424.1	P48637-1V9HWJ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1 linkuse as main transcript	c.1301+190T>C		intron_variant			NM_000178.4	ENSP00000498303.1		P48637-1

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100956

AN:

151888

Hom.:

35060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.865

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.632

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.614

Gnomad OTH

AF:

0.623

GnomAD4 exome

AF:

0.613

AC:

334922

AN:

546274

Hom.:

105723

Cov.:

AF XY:

0.621

AC XY:

181328

AN XY:

291858

show subpopulations

Gnomad4 AFR exome

AF:

0.866

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.639

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.740

Gnomad4 FIN exome

AF:

0.601

Gnomad4 NFE exome

AF:

0.621

Gnomad4 OTH exome

AF:

0.622

GnomAD4 genome

AF:

0.664

AC:

101007

AN:

152006

Hom.:

35085

Cov.:

AF XY:

0.661

AC XY:

49064

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.864

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.632

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.738

Gnomad4 FIN

AF:

0.595

Gnomad4 NFE

AF:

0.614

Gnomad4 OTH

AF:

0.627

Alfa

AF:

0.599

Hom.:

6916

Bravo

AF:

0.655

TwinsUK

AF:

0.611

AC:

2264

ALSPAC

AF:

0.606

AC:

2335

ESP6500AA

AF:

0.865

AC:

1197

ESP6500EA

AF:

0.622

AC:

1978

Asia WGS

AF:

0.619

AC:

2155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.78

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.13

MetaRNN

Benign

0.00074

GERP RS

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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