rs406113

Variant names:

Variant summary

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

The NM_182701.1(GPX6):c.39T>G(p.Phe13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,611,226 control chromosomes in the GnomAD database, including 106,481 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F13C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.44 ( 17024 hom., cov: 31)

Exomes 𝑓: 0.34 ( 89457 hom. )

Consequence

GPX6
NM_182701.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164

Publications

40 publications found

Variant links:

Genes affected

GPX6 (HGNC:4558): (glutathione peroxidase 6) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. Expression of this gene has been observed in embryos and olfactory epithelium; however, the exact function of this gene is not known. This isozyme is a selenoprotein in humans, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. The orthologs of this gene in mouse and rat (and some other species) contain a cysteine (Cys) residue in place of the Sec residue, and their corresponding mRNAs lack SECIS element. [provided by RefSeq, Jul 2017]

GPX6 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 (MetaRNN=3.6888187E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPX6	NM_182701.1 link	c.39T>G	p.Phe13Leu	missense_variant	Exon 1 of 5	ENST00000361902.5	NP_874360.1	P59796

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPX6	ENST00000361902.5 link	c.39T>G	p.Phe13Leu	missense_variant	Exon 1 of 5	1	NM_182701.1	ENSP00000354581.1	P59796
GPX6	ENST00000474923.1 link	c.39T>G	p.Phe13Leu	missense_variant	Exon 1 of 4	1		ENSP00000417364.1	A0A182DWH6
GPX6	ENST00000483058.1 link	n.307-4801T>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67074

AN:

151838

Hom.:

16967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.431

GnomAD2 exomes

AF:

0.377

AC:

94022

AN:

249432

AF XY:

0.365

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.341

AC:

497596

AN:

1459272

Hom.:

89457

Cov.:

AF XY:

0.339

AC XY:

246345

AN XY:

726052

show subpopulations

African (AFR)

AF:

0.712

AC:

23788

AN:

33426

American (AMR)

AF:

0.422

AC:

18876

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8646

AN:

26114

East Asian (EAS)

AF:

0.528

AC:

20959

AN:

39678

South Asian (SAS)

AF:

0.361

AC:

31091

AN:

86182

European-Finnish (FIN)

AF:

0.318

AC:

17002

AN:

53410

Middle Eastern (MID)

AF:

0.293

AC:

1691

AN:

5764

European-Non Finnish (NFE)

AF:

0.319

AC:

354127

AN:

1109698

Other (OTH)

AF:

0.355

AC:

21416

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

16353

32706

49059

65412

81765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11904

23808

35712

47616

59520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.442

AC:

67187

AN:

151954

Hom.:

17024

Cov.:

AF XY:

0.439

AC XY:

32585

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.700

AC:

28981

AN:

41420

American (AMR)

AF:

0.411

AC:

6287

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1079

AN:

3468

East Asian (EAS)

AF:

0.526

AC:

2714

AN:

5160

South Asian (SAS)

AF:

0.365

AC:

1754

AN:

4810

European-Finnish (FIN)

AF:

0.315

AC:

3323

AN:

10552

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21736

AN:

67950

Other (OTH)

AF:

0.427

AC:

901

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1700

3400

5101

6801

8501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.367

Hom.:

33335

Bravo

AF:

0.465

TwinsUK

AF:

0.306

AC:

1135

ALSPAC

AF:

0.329

AC:

1267

ESP6500AA

AF:

0.668

AC:

2639

ESP6500EA

AF:

0.313

AC:

2604

ExAC

AF:

0.379

AC:

45837

Asia WGS

AF:

0.413

AC:

1436

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.81

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0063

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.28

T;T;.

MetaRNN

Benign

0.0000037

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.5

N;.;.

PhyloP100

0.16

PrimateAI

Benign

0.36

PROVEAN

Benign

0.99

N;.;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.026

MutPred

0.41

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MPC

0.12

ClinPred

0.0026

GERP RS

1.5

PromoterAI

0.029

Neutral

(source)

Varity_R

0.027

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over