Variant 15-45135557-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_175940.3(DUOX1):c.579C>G(p.Ser193Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00957 in 1,556,238 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0099 ( 108 hom. )

Consequence

DUOX1
NM_175940.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.888

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 15-45135557-C-G is Benign according to our data. Variant chr15-45135557-C-G is described in ClinVar as [Benign]. Clinvar id is 2645293.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.888 with no splicing effect.

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.579C>G	p.Ser193Ser	synonymous_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.579C>G	p.Ser193Ser	synonymous_variant	6/34	1	NM_175940.3	ENSP00000373689.3	Q9NRD9-1
DUOX1	ENST00000321429.8 linkuse as main transcript	c.579C>G	p.Ser193Ser	synonymous_variant	7/35	1		ENSP00000317997.4	Q9NRD9-1
DUOX1	ENST00000561220.6 linkuse as main transcript	n.579C>G		non_coding_transcript_exon_variant	6/33	5		ENSP00000452623.1	H0YK19

Frequencies

GnomAD3 genomes

AF:

0.00686

AC:

1043

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00464

AC:

743

AN:

160266

Hom.:

AF XY:

0.00456

AC XY:

396

AN XY:

86772

show subpopulations

Gnomad AFR exome

AF:

0.000907

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.000240

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.00546

Gnomad NFE exome

AF:

0.00833

Gnomad OTH exome

AF:

0.00496

GnomAD4 exome

AF:

0.00986

AC:

13849

AN:

1404186

Hom.:

108

Cov.:

AF XY:

0.00949

AC XY:

6584

AN XY:

693932

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.000555

Gnomad4 EAS exome

AF:

0.000245

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.00785

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00831

GnomAD4 genome

AF:

0.00686

AC:

1043

AN:

152052

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

470

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00728

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

DUOX1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.9

DANN

Benign

0.50

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