rs2236271

Variant names:

• chr20-34936037-A-C
• rs2236271
• NM_000178.4:c.768-395T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-34936037-A-C
• chr20-34936037-A-G
• chr20-34936037-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000178.4(GSS):​c.768-395T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,072 control chromosomes in the GnomAD database, including 34,826 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 0.66 (34826 hom., cov: 32)
• Consequence: GSS NM_000178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• inherited glutathione synthetase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• glutathione synthetase deficiency with 5-oxoprolinuria

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSS	NM_000178.4	c.768-395T>G		intron_variant	Intron 8 of 12	ENST00000651619.1	NP_000169.1
GSS	NM_001322494.1	c.768-395T>G		intron_variant	Intron 8 of 12		NP_001309423.1
GSS	NM_001322495.1	c.768-395T>G		intron_variant	Intron 8 of 12		NP_001309424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSS	ENST00000651619.1	c.768-395T>G		intron_variant	Intron 8 of 12		NM_000178.4	ENSP00000498303.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100485 AN: 151954 Hom.: 34799 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.661 AC: 100540 AN: 152072 Hom.: 34826 Cov.: 32 AF XY: 0.656 AC XY: 48753 AN XY: 74326

African (AFR) AF: 0.867 AC: 36004 AN: 41508

American (AMR) AF: 0.469 AC: 7172 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2167 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2332 AN: 5172

South Asian (SAS) AF: 0.736 AC: 3547 AN: 4818

European-Finnish (FIN) AF: 0.567 AC: 5978 AN: 10550

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41409 AN: 67966

Other (OTH) AF: 0.624 AC: 1320 AN: 2114

Alfa AF: 0.550 Hom.: 1956

Bravo AF: 0.654

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.50
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2236271; hg19: chr20-33523840;