rs8177431

Positions:

• chr5-151024435-G-A
• chr5-151024435-G-C
• chr5-151024435-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.88-905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,050 control chromosomes in the GnomAD database, including 22,583 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 0.52 (22583 hom., cov: 31)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

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 (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX3	NM_002084.5	c.88-905G>A		intron_variant		ENST00000388825.9	NP_002075.2
GPX3	NM_001329790.2	c.115-905G>A		intron_variant			NP_001316719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9	c.88-905G>A		intron_variant		1	NM_002084.5	ENSP00000373477	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79526 AN: 151932 Hom.: 22556 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.523 AC: 79596 AN: 152050 Hom.: 22583 Cov.: 31 AF XY: 0.521 AC XY: 38736 AN XY: 74314

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.535

Alfa AF: 0.471 Hom.: 2656

Bravo AF: 0.509

Asia WGS AF: 0.462 AC: 1606 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	1.4
DANN	Benign	0.19

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: rs8177431; hg19: chr5-150403996; COSMIC: COSV66312870; COSMIC: COSV66312870;