Variant 15-45135648-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175940.3(DUOX1):c.670G>A(p.Gly224Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000269 in 1,522,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DUOX1
NM_175940.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19879314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX1	NM_175940.3 linkuse as main transcript	c.670G>A	p.Gly224Arg	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.670G>A	p.Gly224Arg	missense_variant	6/34	1	NM_175940.3	ENSP00000373689.3	Q9NRD9-1
DUOX1	ENST00000321429.8 linkuse as main transcript	c.670G>A	p.Gly224Arg	missense_variant	7/35	1		ENSP00000317997.4	Q9NRD9-1
DUOX1	ENST00000561220.6 linkuse as main transcript	n.670G>A		non_coding_transcript_exon_variant	6/33	5		ENSP00000452623.1	H0YK19

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000100

AC:

AN:

119976

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

64362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000961

Gnomad SAS exome

AF:

0.000504

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000477

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000285

AC:

AN:

1370486

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

673390

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000400

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000469

Gnomad4 OTH exome

AF:

0.0000706

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000509

Hom.:

ExAC

AF:

0.0000226

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.670G>A (p.G224R) alteration is located in exon 7 (coding exon 5) of the DUOX1 gene. This alteration results from a G to A substitution at nucleotide position 670, causing the glycine (G) at amino acid position 224 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.82

.;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.37

Sift

Benign

0.15

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.71

P;P

Vest4

0.35

MutPred

0.54

Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);

MVP

0.85

MPC

0.40

ClinPred

0.12

GERP RS

3.0

Varity_R

0.16

gMVP

0.47

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