rs3763011

chr5-151025142-G-Achr5-151025142-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GPX3	NM_002084.5	c.88-198G>A		intron_variant		ENST00000388825.9
GPX3	NM_001329790.2	c.115-198G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX3	ENST00000388825.9	c.88-198G>A		intron_variant		1	NM_002084.5	P1

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.249

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

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: rs3763011; hg19: chr5-150404703;