5-151022773-C-T

Position:

• chr5-151022773-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002084.5(GPX3):​c.87+2032C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,032 control chromosomes in the GnomAD database, including 31,125 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 0.62 (31125 hom., cov: 31)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX3	NM_002084.5	c.87+2032C>T		intron_variant		ENST00000388825.9
GPX3	NM_001329790.2	c.114+1919C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX3	ENST00000388825.9	c.87+2032C>T		intron_variant		1	NM_002084.5	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93906 AN: 151914 Hom.: 31115 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.618 AC: 93951 AN: 152032 Hom.: 31125 Cov.: 31 AF XY: 0.613 AC XY: 45542 AN XY: 74330

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.626

Alfa AF: 0.717 Hom.: 39287

Bravo AF: 0.599

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs4958872; hg19: chr5-150402334; COSMIC: COSV66312865; COSMIC: COSV66312865;