Variant 15-45134175-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175940.3(DUOX1):c.173G>A(p.Ser58Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,557,834 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 28 hom. )

Consequence

DUOX1
NM_175940.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.204

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010817796).

BP6

Variant 15-45134175-G-A is Benign according to our data. Variant chr15-45134175-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024775.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX1	NM_175940.3 linkuse as main transcript	c.173G>A	p.Ser58Asn	missense_variant	4/34	ENST00000389037.7	NP_787954.1	Q9NRD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUOX1	ENST00000389037.7 linkuse as main transcript	c.173G>A	p.Ser58Asn	missense_variant	4/34	1	NM_175940.3	ENSP00000373689.3	Q9NRD9-1
DUOX1	ENST00000321429.8 linkuse as main transcript	c.173G>A	p.Ser58Asn	missense_variant	5/35	1		ENSP00000317997.4	Q9NRD9-1
DUOX1	ENST00000561220.6 linkuse as main transcript	n.173G>A		non_coding_transcript_exon_variant	4/33	5		ENSP00000452623.1	H0YK19

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

691

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00715

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00467

AC:

938

AN:

200848

Hom.:

AF XY:

0.00487

AC XY:

527

AN XY:

108160

show subpopulations

Gnomad AFR exome

AF:

0.00150

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.00959

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00400

Gnomad FIN exome

AF:

0.00267

Gnomad NFE exome

AF:

0.00676

Gnomad OTH exome

AF:

0.00520

GnomAD4 exome

AF:

0.00684

AC:

9610

AN:

1405578

Hom.:

Cov.:

AF XY:

0.00687

AC XY:

4778

AN XY:

695866

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.00281

Gnomad4 ASJ exome

AF:

0.00797

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00435

Gnomad4 FIN exome

AF:

0.00291

Gnomad4 NFE exome

AF:

0.00777

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.00454

AC:

691

AN:

152256

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

305

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00715

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00632

Hom.:

Bravo

AF:

0.00460

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00486

AC:

590

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

DUOX1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.18

.;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.61

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.11

Sift

Benign

0.92

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.65

MPC

0.28

ClinPred

0.0012

GERP RS

1.9

Varity_R

0.14

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over