rs870406

Variant names:

• chr5-151021040-G-A
• rs870406
• NM_002084.5:c.87+299G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151021040-G-A
• chr5-151021040-G-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+299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 415,042 control chromosomes in the GnomAD database, including 3,184 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 0.10 (886 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2298 hom.)
• Consequence: GPX3 NM_002084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 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+299G>A		intron	N/A	NP_002075.2
	GPX3	NM_001329790.2		c.114+186G>A		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+299G>A		intron	N/A	ENSP00000373477.4	P22352
	GPX3	ENST00000521650.5	TSL:2	c.114+186G>A		intron	N/A	ENSP00000427873.1	E5RG32
	GPX3	ENST00000517973.1	TSL:3	c.87+299G>A		intron	N/A	ENSP00000429709.1	A0A182DWH9

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15190 AN: 152046 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.129 AC: 33994 AN: 262878 Hom.: 2298 Cov.: 0 AF XY: 0.133 AC XY: 18471 AN XY: 139310

African (AFR) AF: 0.0482 AC: 315 AN: 6538

American (AMR) AF: 0.0657 AC: 523 AN: 7960

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 1232 AN: 8294

East Asian (EAS) AF: 0.135 AC: 1746 AN: 12936

South Asian (SAS) AF: 0.155 AC: 5640 AN: 36318

European-Finnish (FIN) AF: 0.109 AC: 1745 AN: 15992

Middle Eastern (MID) AF: 0.197 AC: 300 AN: 1520

European-Non Finnish (NFE) AF: 0.130 AC: 20565 AN: 157758

Other (OTH) AF: 0.124 AC: 1928 AN: 15562

GnomAD4 genome AF: 0.0998 AC: 15186 AN: 152164 Hom.: 886 Cov.: 32 AF XY: 0.0982 AC XY: 7303 AN XY: 74398

African (AFR) AF: 0.0390 AC: 1622 AN: 41540

American (AMR) AF: 0.0737 AC: 1126 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3470

East Asian (EAS) AF: 0.153 AC: 790 AN: 5150

South Asian (SAS) AF: 0.143 AC: 692 AN: 4828

European-Finnish (FIN) AF: 0.104 AC: 1100 AN: 10590

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8899 AN: 67982

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.115 Hom.: 1373

Bravo AF: 0.0924

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.88
PhyloP100		-0.17
PromoterAI		0.085	Neutral
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: rs870406; hg19: chr5-150400601;