rs1303751437

Variant names:

• chr6-52899972-C-A
• NM_000847.5:c.376G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-52899972-C-A
• chr6-52899972-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000847.5(GSTA3):​c.376G>T​(p.Glu126*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GSTA3 NM_000847.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

GSTA3 (HGNC:4628): (glutathione S-transferase alpha 3) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

LOC105375091 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA3	NM_000847.5	c.376G>T	p.Glu126*	stop_gained	Exon 5 of 7	ENST00000211122.4	NP_000838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA3	ENST00000211122.4	c.376G>T	p.Glu126*	stop_gained	Exon 5 of 7	1	NM_000847.5	ENSP00000211122.3
GSTA3	ENST00000370968.5	c.226G>T	p.Glu76*	stop_gained	Exon 4 of 6	1		ENSP00000360007.1
GSTA3	ENST00000431899.2	c.226G>T	p.Glu76*	stop_gained	Exon 3 of 4	5		ENSP00000399142.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.33
Eigen_PC	Benign	-0.00042
FATHMM_MKL	Benign	0.21	N
Vest4		0.80
GERP RS		3.0

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-52764770;