5-151024535-A-G

Variant names:

• chr5-151024535-A-G
• rs4958873
• NM_002084.5:c.88-805A>G

Variant summary

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

The NM_002084.5(GPX3):​c.88-805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,148 control chromosomes in the GnomAD database, including 47,680 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 0.79 (47680 hom., cov: 31)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002084.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	NM_002084.5	MANE Select	c.88-805A>G		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.115-805A>G		intron	N/A	NP_001316719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	ENST00000388825.9	TSL:1 MANE Select	c.88-805A>G		intron	N/A	ENSP00000373477.4
	GPX3	ENST00000521650.5	TSL:2	c.115-805A>G		intron	N/A	ENSP00000427873.1
	GPX3	ENST00000517973.1	TSL:3	c.88-2365A>G		intron	N/A	ENSP00000429709.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119570 AN: 152030 Hom.: 47644 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.786 AC: 119653 AN: 152148 Hom.: 47680 Cov.: 31 AF XY: 0.786 AC XY: 58452 AN XY: 74384

African (AFR) AF: 0.647 AC: 26823 AN: 41472

American (AMR) AF: 0.838 AC: 12821 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2767 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5030 AN: 5172

South Asian (SAS) AF: 0.832 AC: 4009 AN: 4820

European-Finnish (FIN) AF: 0.817 AC: 8664 AN: 10600

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56781 AN: 68000

Other (OTH) AF: 0.786 AC: 1662 AN: 2114

Alfa AF: 0.817 Hom.: 65215

Bravo AF: 0.782

Asia WGS AF: 0.857 AC: 2978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.73
PhyloP100		0.81
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: rs4958873; hg19: chr5-150404096;