NM_002084.5:c.88-1961A>G

Variant names:

• chr5-151023379-A-G
• rs8177426
• NM_002084.5:c.88-1961A>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.88-1961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,010 control chromosomes in the GnomAD database, including 44,792 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 0.76 (44792 hom., cov: 31)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 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.88-1961A>G		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.115-1961A>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.88-1961A>G		intron	N/A	ENSP00000373477.4
	GPX3	ENST00000521650.5	TSL:2	c.115-1961A>G		intron	N/A	ENSP00000427873.1
	GPX3	ENST00000517973.1	TSL:3	c.87+2638A>G		intron	N/A	ENSP00000429709.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115361 AN: 151894 Hom.: 44765 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.759 AC: 115427 AN: 152010 Hom.: 44792 Cov.: 31 AF XY: 0.758 AC XY: 56350 AN XY: 74292

African (AFR) AF: 0.582 AC: 24095 AN: 41386

American (AMR) AF: 0.821 AC: 12548 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2709 AN: 3472

East Asian (EAS) AF: 0.951 AC: 4920 AN: 5172

South Asian (SAS) AF: 0.738 AC: 3550 AN: 4812

European-Finnish (FIN) AF: 0.816 AC: 8625 AN: 10576

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56291 AN: 67994

Other (OTH) AF: 0.763 AC: 1607 AN: 2106

Alfa AF: 0.807 Hom.: 82608

Bravo AF: 0.755

Asia WGS AF: 0.796 AC: 2765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.044
DANN	Benign	0.36
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8177426; hg19: chr5-150402940;