rs3763011

Variant names:

• chr5-151025142-G-A
• rs3763011
• NM_002084.5:c.88-198G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151025142-G-A
• chr5-151025142-G-T

Variant summary

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

The NM_002084.5(GPX3):​c.88-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,782 control chromosomes in the GnomAD database, including 4,988 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 0.24 (4988 hom., cov: 31)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 12 publications found

Genes affected

GPX3 (HGNC:4555): (glutathione peroxidase 3) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is secreted, and is abundantly found in plasma. Downregulation of expression of this gene by promoter hypermethylation has been observed in a wide spectrum of human malignancies, including thyroid cancer, hepatocellular carcinoma and chronic myeloid leukemia. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX3	NM_002084.5	c.88-198G>A		intron_variant	Intron 1 of 4	ENST00000388825.9	NP_002075.2
GPX3	NM_001329790.2	c.115-198G>A		intron_variant	Intron 2 of 5		NP_001316719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9	c.88-198G>A		intron_variant	Intron 1 of 4	1	NM_002084.5	ENSP00000373477.4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36349 AN: 151664 Hom.: 4986 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.240 AC: 36368 AN: 151782 Hom.: 4988 Cov.: 31 AF XY: 0.245 AC XY: 18155 AN XY: 74160

African (AFR) AF: 0.236 AC: 9760 AN: 41356

American (AMR) AF: 0.246 AC: 3747 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3466

East Asian (EAS) AF: 0.623 AC: 3210 AN: 5156

South Asian (SAS) AF: 0.434 AC: 2087 AN: 4808

European-Finnish (FIN) AF: 0.206 AC: 2166 AN: 10502

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13528 AN: 67930

Other (OTH) AF: 0.249 AC: 524 AN: 2108

Alfa AF: 0.134 Hom.: 241

Bravo AF: 0.242

Asia WGS AF: 0.450 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.45
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3763011; hg19: chr5-150404703;