rs2273106

Positions:

• chr6-28532102-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPX5	NM_001509.3	c.359+207A>G		intron_variant		ENST00000412168.7
GPX5	NM_003996.3	c.242-219A>G		intron_variant
GPX5	NR_144470.2	n.438-219A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPX5	ENST00000412168.7	c.359+207A>G		intron_variant		1	NM_001509.3	P1
GPX5	ENST00000469384.1	c.242-219A>G		intron_variant		1
GPX5	ENST00000442674.6	n.734+207A>G		intron_variant, non_coding_transcript_variant		5
GPX5	ENST00000483784.1	n.433-219A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.0996

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.131

Alfa AF: 0.118 Hom.: 430

Bravo AF: 0.133

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.27

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: rs2273106; hg19: chr6-28499879;