5-151022235-A-G

Variant names:

• chr5-151022235-A-G
• rs3828599
• NM_002084.5:c.87+1494A>G

Variant summary

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

The NM_001329790.2(GPX3):​c.114+1381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,098 control chromosomes in the GnomAD database, including 34,830 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 0.67 (34830 hom., cov: 32)
• Consequence: GPX3 NM_001329790.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 48 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 (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329790.2. 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.87+1494A>G		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.114+1381A>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.87+1494A>G		intron	N/A	ENSP00000373477.4
	GPX3	ENST00000521650.5	TSL:2	c.114+1381A>G		intron	N/A	ENSP00000427873.1
	GPX3	ENST00000517973.1	TSL:3	c.87+1494A>G		intron	N/A	ENSP00000429709.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101804 AN: 151980 Hom.: 34801 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.670 AC: 101872 AN: 152098 Hom.: 34830 Cov.: 32 AF XY: 0.663 AC XY: 49301 AN XY: 74340

African (AFR) AF: 0.543 AC: 22506 AN: 41470

American (AMR) AF: 0.665 AC: 10160 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3472

East Asian (EAS) AF: 0.539 AC: 2790 AN: 5172

South Asian (SAS) AF: 0.537 AC: 2589 AN: 4822

European-Finnish (FIN) AF: 0.733 AC: 7756 AN: 10574

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51392 AN: 67994

Other (OTH) AF: 0.660 AC: 1392 AN: 2110

Alfa AF: 0.713 Hom.: 70792

Bravo AF: 0.657

Asia WGS AF: 0.549 AC: 1909 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	2.7
DANN	Benign	0.35
PhyloP100		-0.35
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: rs3828599; hg19: chr5-150401796;