chr6-28510778-A-T

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.214T>A(p.Tyr72Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 1,613,930 control chromosomes in the GnomAD database, including 2,967 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y72C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.049 ( 226 hom., cov: 33)

Exomes 𝑓: 0.057 ( 2741 hom. )

Consequence

GPX6
NM_182701.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.26

Publications

12 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=0.004087776).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182701.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX6	NM_182701.1	MANE Select	c.214T>A	p.Tyr72Asn	missense	Exon 2 of 5	NP_874360.1	P59796

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPX6	ENST00000361902.5	TSL:1 MANE Select	c.214T>A	p.Tyr72Asn	missense	Exon 2 of 5	ENSP00000354581.1	P59796
GPX6	ENST00000474923.1	TSL:1	c.214T>A	p.Tyr72Asn	missense	Exon 2 of 4	ENSP00000417364.1	A0A182DWH6
GPX6	ENST00000483058.1	TSL:4	n.433T>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7495

AN:

152164

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0319

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0715

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0629

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0447

AC:

11143

AN:

249386

AF XY:

0.0439

show subpopulations

Gnomad AFR exome

AF:

0.0376

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00517

Gnomad FIN exome

AF:

0.0761

Gnomad NFE exome

AF:

0.0640

Gnomad OTH exome

AF:

0.0421

GnomAD4 exome

AF:

0.0570

AC:

83286

AN:

1461648

Hom.:

2741

Cov.:

AF XY:

0.0554

AC XY:

40295

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.0375

AC:

1255

AN:

33472

American (AMR)

AF:

0.0251

AC:

1124

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

531

AN:

26134

East Asian (EAS)

AF:

0.00264

AC:

105

AN:

39700

South Asian (SAS)

AF:

0.0104

AC:

901

AN:

86238

European-Finnish (FIN)

AF:

0.0740

AC:

3947

AN:

53322

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0652

AC:

72539

AN:

1111904

Other (OTH)

AF:

0.0470

AC:

2838

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

4160

8319

12479

16638

20798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2668

5336

8004

10672

13340

<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:

0.0492

AC:

7493

AN:

152282

Hom.:

226

Cov.:

AF XY:

0.0483

AC XY:

3597

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0395

AC:

1641

AN:

41552

American (AMR)

AF:

0.0319

AC:

488

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.00541

AC:

AN:

5178

South Asian (SAS)

AF:

0.0141

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0715

AC:

759

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0629

AC:

4280

AN:

68018

Other (OTH)

AF:

0.0388

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

358

716

1075

1433

1791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0545

Hom.:

185

Bravo

AF:

0.0472

TwinsUK

AF:

0.0636

AC:

236

ALSPAC

AF:

0.0656

AC:

253

ESP6500AA

AF:

0.0397

AC:

160

ESP6500EA

AF:

0.0620

AC:

517

ExAC

AF:

0.0458

AC:

5539

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0519

EpiControl

AF:

0.0576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0096

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

PhyloP100

8.3

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.46

MPC

0.65

ClinPred

0.070

GERP RS

4.1

Varity_R

0.51

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over