Variant 15-45135558-A-G 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.580A>G(p.Arg194Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00948 in 1,555,880 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0098 ( 108 hom. )

Consequence

DUOX1
NM_175940.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71

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=0.009414524).

BP6

Variant 15-45135558-A-G is Benign according to our data. Variant chr15-45135558-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645294.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX1	NM_175940.3 linkuse as main transcript	c.580A>G	p.Arg194Gly	missense_variant	6/34	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.580A>G	p.Arg194Gly	missense_variant	6/34	1	NM_175940.3	ENSP00000373689.3	Q9NRD9-1
DUOX1	ENST00000321429.8 linkuse as main transcript	c.580A>G	p.Arg194Gly	missense_variant	7/35	1		ENSP00000317997.4	Q9NRD9-1
DUOX1	ENST00000561220.6 linkuse as main transcript	n.580A>G		non_coding_transcript_exon_variant	6/33	5		ENSP00000452623.1	H0YK19

Frequencies

GnomAD3 genomes

AF:

0.00697

AC:

1058

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00473

AC:

761

AN:

160782

Hom.:

AF XY:

0.00471

AC XY:

410

AN XY:

87094

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00378

Gnomad ASJ exome

AF:

0.000240

Gnomad EAS exome

AF:

0.0000809

Gnomad SAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.00539

Gnomad NFE exome

AF:

0.00819

Gnomad OTH exome

AF:

0.00517

GnomAD4 exome

AF:

0.00976

AC:

13696

AN:

1403874

Hom.:

108

Cov.:

AF XY:

0.00940

AC XY:

6524

AN XY:

693804

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.000555

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00200

Gnomad4 FIN exome

AF:

0.00781

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00822

GnomAD4 genome

AF:

0.00696

AC:

1058

AN:

152006

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

477

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00230

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00669

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00279

Hom.:

ExAC

AF:

0.00207

AC:

238

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

Dec 01, 2022

DUOX1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.061

.;T

MetaRNN

Benign

0.0094

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.3

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

2.5

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.11

MVP

0.57

MPC

0.38

ClinPred

0.0015

GERP RS

4.0

Varity_R

0.18

gMVP

0.42

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