rs2236270

chr20-34935352-G-T

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.834+224C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,052 control chromosomes in the GnomAD database, including 8,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8685 hom., cov: 32)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20

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=-0.77).
• BP6: Variant 20-34935352-G-T is Benign according to our data. Variant chr20-34935352-G-T is described in ClinVar as [Benign]. Clinvar id is 1181524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSS	NM_000178.4	c.834+224C>A		intron_variant		ENST00000651619.1
GSS	NM_001322494.1	c.834+224C>A		intron_variant
GSS	NM_001322495.1	c.834+224C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSS	ENST00000651619.1	c.834+224C>A		intron_variant			NM_000178.4	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49799 AN: 151936 Hom.: 8684 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49804 AN: 152052 Hom.: 8685 Cov.: 32 AF XY: 0.327 AC XY: 24293 AN XY: 74334

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.344

Alfa AF: 0.378 Hom.: 10576

Bravo AF: 0.314

Asia WGS AF: 0.266 AC: 929 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	13
Dann	Benign	0.81

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: rs2236270; hg19: chr20-33523155; COSMIC: COSV53814752; COSMIC: COSV53814752;