5-151023009-A-G

Position:

• chr5-151023009-A-G

Variant summary

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

The NM_002084.5(GPX3):​c.87+2268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,988 control chromosomes in the GnomAD database, including 46,492 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 0.77 (46492 hom., cov: 30)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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]

GPX3 (HGNC:):

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 = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX3	NM_002084.5	c.87+2268A>G		intron_variant		ENST00000388825.9	NP_002075.2
GPX3	NM_001329790.2	c.114+2155A>G		intron_variant			NP_001316719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX3	ENST00000388825.9	c.87+2268A>G		intron_variant		1	NM_002084.5	ENSP00000373477.4

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117662 AN: 151870 Hom.: 46459 Cov.: 30

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.775 AC: 117743 AN: 151988 Hom.: 46492 Cov.: 30 AF XY: 0.775 AC XY: 57567 AN XY: 74306

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.782

Alfa AF: 0.823 Hom.: 52494

Bravo AF: 0.768

Asia WGS AF: 0.855 AC: 2969 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.52

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: rs4958434; hg19: chr5-150402570;