rs2273684

Positions:

• chr20-34941963-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000178.4(GSS):​c.492-134A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 724,288 control chromosomes in the GnomAD database, including 80,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (21260 hom., cov: 31)
  • Exomes 𝑓: 0.45 (59638 hom.)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-34941963-T-G is Benign according to our data. Variant chr20-34941963-T-G is described in ClinVar as [Benign]. Clinvar id is 1224925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSS	NM_000178.4	c.492-134A>C		intron_variant		ENST00000651619.1
GSS	NM_001322494.1	c.492-134A>C		intron_variant
GSS	NM_001322495.1	c.492-134A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSS	ENST00000651619.1	c.492-134A>C		intron_variant			NM_000178.4	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77595 AN: 151814 Hom.: 21236 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.445 AC: 254943 AN: 572356 Hom.: 59638 AF XY: 0.447 AC XY: 139999 AN XY: 312902

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.511 AC: 77648 AN: 151932 Hom.: 21260 Cov.: 31 AF XY: 0.508 AC XY: 37730 AN XY: 74252

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.490

Alfa AF: 0.463 Hom.: 23803

Bravo AF: 0.510

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs2273684; hg19: chr20-33529766;