20-34928268-T-C

Variant names:

• chr20-34928268-T-C
• rs725521
• NM_000178.4:c.*560A>G

Variant summary

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

The NM_000178.4(GSS):​c.*560A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,906 control chromosomes in the GnomAD database, including 23,093 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 (23093 hom., cov: 31)
• Consequence: GSS NM_000178.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSS	NM_000178.4	c.*560A>G		downstream_gene_variant		ENST00000651619.1	NP_000169.1
GSS	NM_001322494.1	c.*560A>G		downstream_gene_variant			NP_001309423.1
GSS	NM_001322495.1	c.*560A>G		downstream_gene_variant			NP_001309424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1	c.*560A>G		downstream_gene_variant			NM_000178.4	ENSP00000498303.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82396 AN: 151788 Hom.: 23080 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.543 AC: 82418 AN: 151906 Hom.: 23093 Cov.: 31 AF XY: 0.542 AC XY: 40232 AN XY: 74230

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.539

Alfa AF: 0.576 Hom.: 3745

Bravo AF: 0.518

Asia WGS AF: 0.595 AC: 2072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs725521; hg19: chr20-33516071;