NM_002084.5:c.87+2188G>C

Variant names:

• chr5-151022929-G-C
• rs3792796
• NM_002084.5:c.87+2188G>C

Variant summary

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

The NM_002084.5(GPX3):​c.87+2188G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,932 control chromosomes in the GnomAD database, including 21,179 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 0.50 (21179 hom., cov: 30)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	NM_002084.5	MANE Select	c.87+2188G>C		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.114+2075G>C		intron	N/A	NP_001316719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	ENST00000388825.9	TSL:1 MANE Select	c.87+2188G>C		intron	N/A	ENSP00000373477.4
	GPX3	ENST00000521650.5	TSL:2	c.114+2075G>C		intron	N/A	ENSP00000427873.1
	GPX3	ENST00000517973.1	TSL:3	c.87+2188G>C		intron	N/A	ENSP00000429709.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75933 AN: 151814 Hom.: 21169 Cov.: 30

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.500 AC: 75956 AN: 151932 Hom.: 21179 Cov.: 30 AF XY: 0.497 AC XY: 36881 AN XY: 74264

African (AFR) AF: 0.249 AC: 10319 AN: 41440

American (AMR) AF: 0.573 AC: 8749 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1794 AN: 5138

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6466 AN: 10550

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43135 AN: 67940

Other (OTH) AF: 0.511 AC: 1079 AN: 2110

Alfa AF: 0.599 Hom.: 15656

Bravo AF: 0.486

Asia WGS AF: 0.389 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.37
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: rs3792796; hg19: chr5-150402490; COSMIC: COSV66312867; COSMIC: COSV66312867;