15-45135593-T-C

Position:

• chr15-45135593-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_175940.3(DUOX1):​c.615T>C​(p.Phe205Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUOX1 NM_175940.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.934

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 15-45135593-T-C is Benign according to our data. Variant chr15-45135593-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.934 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX1	NM_175940.3	c.615T>C	p.Phe205Phe	synonymous_variant	6/34	ENST00000389037.7	NP_787954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7	c.615T>C	p.Phe205Phe	synonymous_variant	6/34	1	NM_175940.3	ENSP00000373689.3
DUOX1	ENST00000321429.8	c.615T>C	p.Phe205Phe	synonymous_variant	7/35	1		ENSP00000317997.4
DUOX1	ENST00000561220.6	n.615T>C		non_coding_transcript_exon_variant	6/33	5		ENSP00000452623.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 386 AN: 151574 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.000756

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.000964

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00128 AC: 1801 AN: 1404432 Hom.: 23 Cov.: 34 AF XY: 0.00124 AC XY: 863 AN XY: 694514

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.000584

Gnomad4 ASJ exome AF: 0.0000396

Gnomad4 EAS exome AF: 0.000269

Gnomad4 SAS exome AF: 0.000793

Gnomad4 FIN exome AF: 0.00168

Gnomad4 NFE exome AF: 0.00134

Gnomad4 OTH exome AF: 0.00196

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00255 AC: 387 AN: 151690 Hom.: 0 Cov.: 31 AF XY: 0.00195 AC XY: 145 AN XY: 74180

Gnomad4 AFR AF: 0.00254

Gnomad4 AMR AF: 0.000982

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.000756

Gnomad4 NFE AF: 0.00366

Gnomad4 OTH AF: 0.000954

Alfa AF: 0.00320 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs2258993; hg19: chr15-45427791;