rs2273106

Variant names:

• chr6-28532102-A-G
• rs2273106
• NM_001509.3:c.359+207A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001509.3(GPX5):​c.359+207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,044 control chromosomes in the GnomAD database, including 1,643 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 0.13 (1643 hom., cov: 31)
• Consequence: GPX5 NM_001509.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 3 publications found

Genes affected

GPX5 (HGNC:4557): (glutathione peroxidase 5) This gene belongs to the glutathione peroxidase family. It is specifically expressed in the epididymis in the mammalian male reproductive tract, and is androgen-regulated. Unlike several other characterized glutathione peroxidases, this enzyme is not a selenoprotein, lacking the selenocysteine residue. Thus, it is selenium-independent, and has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001509.3. 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
	GPX5	NM_001509.3	MANE Select	c.359+207A>G		intron	N/A	NP_001500.1	O75715-1
	GPX5	NM_003996.3		c.242-219A>G		intron	N/A	NP_003987.2	O75715-2
	GPX5	NR_144470.2		n.438-219A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX5	ENST00000412168.7	TSL:1 MANE Select	c.359+207A>G		intron	N/A	ENSP00000392398.2	O75715-1
	GPX5	ENST00000469384.1	TSL:1	c.242-219A>G		intron	N/A	ENSP00000419935.1	O75715-2
	GPX5	ENST00000442674.6	TSL:5	n.734+207A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19698 AN: 151926 Hom.: 1630 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.130 AC: 19742 AN: 152044 Hom.: 1643 Cov.: 31 AF XY: 0.134 AC XY: 9986 AN XY: 74320

African (AFR) AF: 0.118 AC: 4906 AN: 41476

American (AMR) AF: 0.181 AC: 2773 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2155 AN: 5116

South Asian (SAS) AF: 0.274 AC: 1317 AN: 4808

European-Finnish (FIN) AF: 0.0996 AC: 1056 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6554 AN: 67976

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.125 Hom.: 864

Bravo AF: 0.133

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.27
PhyloP100		-0.27
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: rs2273106; hg19: chr6-28499879;