chr20-34952197-G-A

Position:

• chr20-34952197-G-A

Variant summary

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

The NM_000178.4(GSS):​c.-8-337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 374,418 control chromosomes in the GnomAD database, including 7,926 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 0.19 (2841 hom., cov: 33)
  • Exomes 𝑓: 0.21 (5085 hom.)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSS	NM_000178.4	c.-8-337C>T		intron_variant		ENST00000651619.1	NP_000169.1
GSS	NM_001322494.1	c.-8-337C>T		intron_variant			NP_001309423.1
GSS	NM_001322495.1	c.-8-337C>T		intron_variant			NP_001309424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1	c.-8-337C>T		intron_variant			NM_000178.4	ENSP00000498303	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28904 AN: 152042 Hom.: 2838 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.208 AC: 46306 AN: 222256 Hom.: 5085 Cov.: 0 AF XY: 0.214 AC XY: 25563 AN XY: 119234

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.190 AC: 28912 AN: 152162 Hom.: 2841 Cov.: 33 AF XY: 0.190 AC XY: 14156 AN XY: 74360

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.205

Alfa AF: 0.184 Hom.: 491

Bravo AF: 0.186

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.72

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: rs2025096; hg19: chr20-33540000;