15-45153958-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_175940.3(DUOX1):c.3532C>T(p.Leu1178Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,608,952 control chromosomes in the GnomAD database, including 348,393 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27050 hom., cov: 29)

Exomes 𝑓: 0.66 ( 321343 hom. )

Consequence

DUOX1
NM_175940.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.584

Publications

41 publications found

Variant links:

Genes affected

DUOX1 (HGNC:3062): (dual oxidase 1) The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes proteins encoded by this gene and the similar DUOX2 gene. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain. This protein generates hydrogen peroxide and thereby plays a role in the activity of thyroid peroxidase, lactoperoxidase, and in lactoperoxidase-mediated antimicrobial defense at mucosal surfaces. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2012]

DUOX1 links:

ENSG00000259539 (HGNC:):

ENSG00000259539 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4798455E-6).

BP6

Variant 15-45153958-C-T is Benign according to our data. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45153958-C-T is described in CliVar as Benign. Clinvar id is 1301432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX1	NM_175940.3 link	c.3532C>T	p.Leu1178Phe	missense_variant	Exon 27 of 34	ENST00000389037.7	NP_787954.1	Q9NRD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7 link	c.3532C>T	p.Leu1178Phe	missense_variant	Exon 27 of 34	1	NM_175940.3	ENSP00000373689.3		Q9NRD9-1

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

88706

AN:

151438

Hom.:

27054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.673

Gnomad OTH

AF:

0.602

GnomAD2 exomes

AF:

0.619

AC:

155532

AN:

251390

AF XY:

0.632

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.592

Gnomad EAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.660

AC:

962361

AN:

1457398

Hom.:

321343

Cov.:

AF XY:

0.662

AC XY:

480428

AN XY:

725294

show subpopulations

African (AFR)

AF:

0.408

AC:

13615

AN:

33380

American (AMR)

AF:

0.509

AC:

22756

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

15371

AN:

26080

East Asian (EAS)

AF:

0.494

AC:

19611

AN:

39684

South Asian (SAS)

AF:

0.704

AC:

60701

AN:

86170

European-Finnish (FIN)

AF:

0.657

AC:

35067

AN:

53398

Middle Eastern (MID)

AF:

0.605

AC:

3483

AN:

5758

European-Non Finnish (NFE)

AF:

0.680

AC:

753430

AN:

1108008

Other (OTH)

AF:

0.636

AC:

38327

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

16332

32664

48996

65328

81660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19204

38408

57612

76816

96020

<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:

0.585

AC:

88725

AN:

151554

Hom.:

27050

Cov.:

AF XY:

0.589

AC XY:

43574

AN XY:

73992

show subpopulations

African (AFR)

AF:

0.417

AC:

17202

AN:

41248

American (AMR)

AF:

0.580

AC:

8841

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

2031

AN:

3472

East Asian (EAS)

AF:

0.476

AC:

2445

AN:

5136

South Asian (SAS)

AF:

0.717

AC:

3443

AN:

4804

European-Finnish (FIN)

AF:

0.659

AC:

6856

AN:

10406

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.673

AC:

45731

AN:

67922

Other (OTH)

AF:

0.600

AC:

1265

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1735

3470

5206

6941

8676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.633

Hom.:

87523

Bravo

AF:

0.567

TwinsUK

AF:

0.683

AC:

2534

ALSPAC

AF:

0.683

AC:

2632

ESP6500AA

AF:

0.425

AC:

1870

ESP6500EA

AF:

0.676

AC:

5814

ExAC

AF:

0.625

AC:

75835

Asia WGS

AF:

0.610

AC:

2125

AN:

3478

EpiCase

AF:

0.671

EpiControl

AF:

0.669

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 22, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.036

.;T;T

MetaRNN

Benign

0.0000025

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.63

N;N;.

PhyloP100

0.58

PrimateAI

Benign

0.44

PROVEAN

Benign

0.42

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.078

MPC

0.32

ClinPred

0.0057

GERP RS

3.4

Varity_R

0.041

gMVP

0.15

Mutation Taster

=96/4

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over