6-28531459-A-C

Variant names:

• chr6-28531459-A-C
• rs440481
• NM_001509.3:c.242-319A>C

Variant summary

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

The NM_001509.3(GPX5):​c.242-319A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 149,212 control chromosomes in the GnomAD database, including 5,465 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 0.25 (5465 hom., cov: 29)
• Consequence: GPX5 NM_001509.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 4 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 = 0.473 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX5	NM_001509.3	MANE Select	c.242-319A>C		intron	N/A	NP_001500.1
	GPX5	NM_003996.3		c.242-862A>C		intron	N/A	NP_003987.2
	GPX5	NR_144470.2		n.438-862A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX5	ENST00000412168.7	TSL:1 MANE Select	c.242-319A>C		intron	N/A	ENSP00000392398.2
	GPX5	ENST00000469384.1	TSL:1	c.242-862A>C		intron	N/A	ENSP00000419935.1
	GPX5	ENST00000442674.6	TSL:5	n.617-319A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.247 AC: 36850 AN: 149098 Hom.: 5441 Cov.: 29

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.247 AC: 36929 AN: 149212 Hom.: 5465 Cov.: 29 AF XY: 0.250 AC XY: 18170 AN XY: 72800

African (AFR) AF: 0.377 AC: 15236 AN: 40362

American (AMR) AF: 0.252 AC: 3766 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 634 AN: 3446

East Asian (EAS) AF: 0.490 AC: 2426 AN: 4956

South Asian (SAS) AF: 0.329 AC: 1528 AN: 4638

European-Finnish (FIN) AF: 0.162 AC: 1651 AN: 10200

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 10943 AN: 67386

Other (OTH) AF: 0.237 AC: 492 AN: 2076

Alfa AF: 0.143 Hom.: 397

Bravo AF: 0.267

Asia WGS AF: 0.363 AC: 1262 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.13
PhyloP100		0.051
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: rs440481; hg19: chr6-28499236;