20-34954802-T-C

Position:

• chr20-34954802-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.-9+925A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 153,802 control chromosomes in the GnomAD database, including 59,450 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 0.88 (58908 hom., cov: 31)
  • Exomes 𝑓: 0.83 (542 hom.)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSS	NM_000178.4	c.-9+925A>G		intron_variant		ENST00000651619.1	NP_000169.1
GSS	NM_001322495.1	c.-95A>G		5_prime_UTR_variant	1/13		NP_001309424.1
GSS	NM_001322494.1	c.-9+1068A>G		intron_variant			NP_001309423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1	c.-9+925A>G		intron_variant			NM_000178.4	ENSP00000498303	P1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133339 AN: 152114 Hom.: 58842 Cov.: 31

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.831 AC: 1304 AN: 1570 Hom.: 542 Cov.: 0 AF XY: 0.831 AC XY: 680 AN XY: 818

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.830

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.877 AC: 133465 AN: 152232 Hom.: 58908 Cov.: 31 AF XY: 0.879 AC XY: 65451 AN XY: 74432

Gnomad4 AFR AF: 0.969

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.843

Alfa AF: 0.846 Hom.: 33403

Bravo AF: 0.881

Asia WGS AF: 0.974 AC: 3387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.7
DANN	Benign	0.84

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: rs6088659; hg19: chr20-33542605;