rs6060124

chr20-34949094-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000178.4(GSS):c.129+2630G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,896 control chromosomes in the GnomAD database, including 5,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5864 hom., cov: 32)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSS	NM_000178.4	c.129+2630G>T		intron_variant		ENST00000651619.1
GSS	NM_001322494.1	c.129+2630G>T		intron_variant
GSS	NM_001322495.1	c.129+2630G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSS	ENST00000651619.1	c.129+2630G>T		intron_variant			NM_000178.4	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41070 AN: 151778 Hom.: 5863 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.270 AC: 41084 AN: 151896 Hom.: 5864 Cov.: 32 AF XY: 0.266 AC XY: 19776 AN XY: 74236

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.235

Alfa AF: 0.268 Hom.: 7388

Bravo AF: 0.264

Asia WGS AF: 0.246 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.3
Dann	Benign	0.44

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: rs6060124; hg19: chr20-33536897;