6-28526550-A-G

Position:

• chr6-28526550-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.87+450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,894 control chromosomes in the GnomAD database, including 12,425 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 0.39 (12425 hom., cov: 31)
• Consequence: GPX5 NM_001509.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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]

GPX6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPX5	NM_001509.3	c.87+450A>G		intron_variant		ENST00000412168.7	NP_001500.1
GPX5	NM_003996.3	c.87+450A>G		intron_variant			NP_003987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPX5	ENST00000412168.7	c.87+450A>G		intron_variant		1	NM_001509.3	ENSP00000392398.2
GPX5	ENST00000469384.1	c.87+450A>G		intron_variant		1		ENSP00000419935.1
GPX6	ENST00000483058.1	n.306+477T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58905 AN: 151774 Hom.: 12392 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.388 AC: 59003 AN: 151894 Hom.: 12425 Cov.: 31 AF XY: 0.387 AC XY: 28749 AN XY: 74216

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.370

Alfa AF: 0.317 Hom.: 8647

Bravo AF: 0.402

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	11
DANN	Benign	0.64

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: rs445870; hg19: chr6-28494327;