20-34935066-T-C

Position:

• chr20-34935066-T-C

Variant summary

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

The NM_000178.4(GSS):​c.834+510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,014 control chromosomes in the GnomAD database, including 23,043 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 0.54 (23043 hom., cov: 31)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSS	NM_000178.4	c.834+510A>G		intron_variant		ENST00000651619.1	NP_000169.1
GSS	NM_001322494.1	c.834+510A>G		intron_variant			NP_001309423.1
GSS	NM_001322495.1	c.834+510A>G		intron_variant			NP_001309424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1	c.834+510A>G		intron_variant			NM_000178.4	ENSP00000498303.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82342 AN: 151896 Hom.: 23035 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.542 AC: 82352 AN: 152014 Hom.: 23043 Cov.: 31 AF XY: 0.541 AC XY: 40196 AN XY: 74290

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.538

Alfa AF: 0.582 Hom.: 3264

Bravo AF: 0.517

Asia WGS AF: 0.591 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.55

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: rs6119545; hg19: chr20-33522869;