chr5-151028379-G-T

Variant names:

• chr5-151028379-G-T
• rs2070593
• NM_002084.5:c.*249G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002084.5(GPX3):​c.*249G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPX3 NM_002084.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 34 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.*249G>T		3_prime_UTR	Exon 5 of 5	NP_002075.2
	GPX3	NM_001329790.2		c.*249G>T		3_prime_UTR	Exon 6 of 6	NP_001316719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX3	ENST00000388825.9	TSL:1 MANE Select	c.*249G>T		3_prime_UTR	Exon 5 of 5	ENSP00000373477.4
	GPX3	ENST00000521632.1	TSL:5	c.*215G>T		3_prime_UTR	Exon 3 of 3	ENSP00000430743.2
	GPX3	ENST00000517973.1	TSL:3	c.*473G>T		downstream_gene	N/A	ENSP00000429709.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 360998 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 190192

African (AFR) AF: 0.00 AC: 0 AN: 10660

American (AMR) AF: 0.00 AC: 0 AN: 15328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11188

East Asian (EAS) AF: 0.00 AC: 0 AN: 23780

South Asian (SAS) AF: 0.00 AC: 0 AN: 44136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 211704

Other (OTH) AF: 0.00 AC: 0 AN: 20792

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.030
DANN	Benign	0.69
PhyloP100		-3.0

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: rs2070593; hg19: chr5-150407940;