5-151028268-T-G

Variant names:

• chr5-151028268-T-G
• rs2230303
• NM_002084.5:c.*138T>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.*138T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 750,716 control chromosomes in the GnomAD database, including 1,315 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 0.056 (602 hom., cov: 33)
  • Exomes 𝑓: 0.024 (713 hom.)
• Consequence: GPX3 NM_002084.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 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.*138T>G		3_prime_UTR	Exon 5 of 5	NP_002075.2
	GPX3	NM_001329790.2		c.*138T>G		3_prime_UTR	Exon 6 of 6	NP_001316719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	ENST00000388825.9	TSL:1 MANE Select	c.*138T>G		3_prime_UTR	Exon 5 of 5	ENSP00000373477.4	P22352
	GPX3	ENST00000521632.1	TSL:5	c.*104T>G		3_prime_UTR	Exon 3 of 3	ENSP00000430743.2	H0YC19
	GPX3	ENST00000517973.1	TSL:3	c.*362T>G		downstream_gene	N/A	ENSP00000429709.1	A0A182DWH9

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8508 AN: 152142 Hom.: 602 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00734

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0245 AC: 14652 AN: 598456 Hom.: 713 Cov.: 8 AF XY: 0.0270 AC XY: 8433 AN XY: 312808

African (AFR) AF: 0.159 AC: 2577 AN: 16242

American (AMR) AF: 0.0201 AC: 604 AN: 30038

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 326 AN: 16402

East Asian (EAS) AF: 0.0783 AC: 2506 AN: 32000

South Asian (SAS) AF: 0.0891 AC: 4841 AN: 54302

European-Finnish (FIN) AF: 0.00131 AC: 47 AN: 36012

Middle Eastern (MID) AF: 0.0323 AC: 128 AN: 3958

European-Non Finnish (NFE) AF: 0.00715 AC: 2705 AN: 378222

Other (OTH) AF: 0.0293 AC: 918 AN: 31280

GnomAD4 genome AF: 0.0560 AC: 8525 AN: 152260 Hom.: 602 Cov.: 33 AF XY: 0.0552 AC XY: 4113 AN XY: 74450

African (AFR) AF: 0.164 AC: 6815 AN: 41514

American (AMR) AF: 0.0289 AC: 443 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5184

South Asian (SAS) AF: 0.0971 AC: 468 AN: 4822

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10628

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00734 AC: 499 AN: 68020

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Alfa AF: 0.0222 Hom.: 624

Bravo AF: 0.0605

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		-0.43
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230303;

hg19: chr5-150407829;