rs451774

Positions:

• chr6-28534773-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.*606A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,036 control chromosomes in the GnomAD database, including 15,797 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 0.42 (15795 hom., cov: 31)
  • Exomes 𝑓: 0.25 (2 hom.)
• Consequence: GPX5 NM_001509.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX5	NM_001509.3	c.*606A>G		3_prime_UTR_variant	5/5	ENST00000412168.7	NP_001500.1
GPX5	NM_003996.3	c.*851A>G		3_prime_UTR_variant	4/4		NP_003987.2
GPX5	NR_144470.2	n.1350A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX5	ENST00000412168.7	c.*606A>G		3_prime_UTR_variant	5/5	1	NM_001509.3	ENSP00000392398	P1
GPX5	ENST00000442674.6	n.1647A>G		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63589 AN: 151886 Hom.: 15742 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 2 Cov.: 0 AF XY: 0.350 AC XY: 7 AN XY: 20

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.214

GnomAD4 genome AF: 0.419 AC: 63703 AN: 152004 Hom.: 15795 Cov.: 31 AF XY: 0.417 AC XY: 31011 AN XY: 74300

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.415

Alfa AF: 0.309 Hom.: 13006

Bravo AF: 0.443

Asia WGS AF: 0.403 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.47

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: rs451774; hg19: chr6-28502550;