dbSNP rs451774: GPX5:c.*606A>G (chr6-28534773-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

19 publications found

Variant links:

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]

GPX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
GPX5	NM_001509.3 link	c.*606A>G	3_prime_UTR_variant	Exon 5 of 5	ENST00000412168.7	NP_001500.1
GPX5	NR_144470.2 link	n.1350A>G	non_coding_transcript_exon_variant	Exon 4 of 4
GPX5	NM_003996.3 link	c.*851A>G	3_prime_UTR_variant	Exon 4 of 4		NP_003987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPX5	ENST00000412168.7 link	c.*606A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_001509.3	ENSP00000392398.2
GPX5	ENST00000442674.6 link	n.1647A>G		non_coding_transcript_exon_variant	Exon 6 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63589

AN:

151886

Hom.:

15742

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.350

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.214

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.638

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.419

AC:

63703

AN:

152004

Hom.:

15795

Cov.:

AF XY:

0.417

AC XY:

31011

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.693

AC:

28718

AN:

41464

American (AMR)

AF:

0.387

AC:

5904

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1021

AN:

3470

East Asian (EAS)

AF:

0.515

AC:

2649

AN:

5142

South Asian (SAS)

AF:

0.356

AC:

1716

AN:

4816

European-Finnish (FIN)

AF:

0.294

AC:

3100

AN:

10558

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19395

AN:

67968

Other (OTH)

AF:

0.415

AC:

876

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1656

3313

4969

6626

8282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.330

Hom.:

37968

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

(source)

DANN

Benign

0.47

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over