5-151027895-T-C

Variant names:

• chr5-151027895-T-C
• rs8177447
• NM_002084.5:c.460-14T>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.460-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,609,620 control chromosomes in the GnomAD database, including 556,179 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 0.79 (47735 hom., cov: 31)
  • Exomes 𝑓: 0.83 (508444 hom.)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 25 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 (REVEL=0.005).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 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.460-14T>C		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.487-14T>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.460-14T>C		intron	N/A	ENSP00000373477.4	P22352
	GPX3	ENST00000520059.1	TSL:3	c.224T>C	p.Leu75Ser	missense	Exon 3 of 3	ENSP00000429314.1	H0YBE4
	GPX3	ENST00000521632.1	TSL:5	c.267-14T>C		intron	N/A	ENSP00000430743.2	H0YC19

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119651 AN: 151986 Hom.: 47699 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.787

GnomAD2 exomes AF: 0.837 AC: 208560 AN: 249148 AF XY: 0.836

Gnomad AFR exome AF: 0.647

Gnomad AMR exome AF: 0.898

Gnomad ASJ exome AF: 0.804

Gnomad EAS exome AF: 0.976

Gnomad FIN exome AF: 0.819

Gnomad NFE exome AF: 0.831

Gnomad OTH exome AF: 0.834

GnomAD4 exome AF: 0.834 AC: 1215701 AN: 1457516 Hom.: 508444 Cov.: 32 AF XY: 0.834 AC XY: 605174 AN XY: 725410

African (AFR) AF: 0.646 AC: 21547 AN: 33348

American (AMR) AF: 0.890 AC: 39803 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 20985 AN: 26106

East Asian (EAS) AF: 0.981 AC: 38945 AN: 39686

South Asian (SAS) AF: 0.830 AC: 71519 AN: 86176

European-Finnish (FIN) AF: 0.821 AC: 43832 AN: 53404

Middle Eastern (MID) AF: 0.833 AC: 4789 AN: 5750

European-Non Finnish (NFE) AF: 0.835 AC: 924940 AN: 1108066

Other (OTH) AF: 0.819 AC: 49341 AN: 60264

GnomAD4 genome AF: 0.787 AC: 119733 AN: 152104 Hom.: 47735 Cov.: 31 AF XY: 0.787 AC XY: 58520 AN XY: 74356

African (AFR) AF: 0.648 AC: 26856 AN: 41472

American (AMR) AF: 0.839 AC: 12833 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2779 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5035 AN: 5170

South Asian (SAS) AF: 0.836 AC: 4026 AN: 4814

European-Finnish (FIN) AF: 0.818 AC: 8658 AN: 10586

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56774 AN: 67970

Other (OTH) AF: 0.788 AC: 1668 AN: 2116

Alfa AF: 0.816 Hom.: 148161

Bravo AF: 0.782

Asia WGS AF: 0.860 AC: 2989 AN: 3478

EpiCase AF: 0.835

EpiControl AF: 0.835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.73
PhyloP100		-0.47
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: rs8177447; hg19: chr5-150407456;