rs870406

Positions:

• chr5-151021040-G-A
• chr5-151021040-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000388825.9(GPX3):​c.87+299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 415,042 control chromosomes in the GnomAD database, including 3,184 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 0.10 (886 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2298 hom.)
• Consequence: GPX3 ENST00000388825.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX3	NM_002084.5	c.87+299G>A		intron_variant		ENST00000388825.9	NP_002075.2
GPX3	NM_001329790.2	c.114+186G>A		intron_variant			NP_001316719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9	c.87+299G>A		intron_variant		1	NM_002084.5	ENSP00000373477	P1

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15190 AN: 152046 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.129 AC: 33994 AN: 262878 Hom.: 2298 Cov.: 0 AF XY: 0.133 AC XY: 18471 AN XY: 139310

Gnomad4 AFR exome AF: 0.0482

Gnomad4 AMR exome AF: 0.0657

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.0998 AC: 15186 AN: 152164 Hom.: 886 Cov.: 32 AF XY: 0.0982 AC XY: 7303 AN XY: 74398

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.105

Alfa AF: 0.119 Hom.: 1120

Bravo AF: 0.0924

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.88

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: rs870406; hg19: chr5-150400601;