NM_175940.3:c.579C>G

Variant names:

• chr15-45135557-C-G
• rs397834845
• NM_175940.3:c.579C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.888
• Publications: 1 publications found

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]

ENSG00000300788 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175940.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX1	NM_175940.3	MANE Select	c.579C>G	p.Ser193Ser	synonymous	Exon 6 of 34	NP_787954.1	Q9NRD9-1
	DUOX1	NM_017434.5		c.579C>G	p.Ser193Ser	synonymous	Exon 7 of 35	NP_059130.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX1	ENST00000389037.7	TSL:1 MANE Select	c.579C>G	p.Ser193Ser	synonymous	Exon 6 of 34	ENSP00000373689.3	Q9NRD9-1
	DUOX1	ENST00000321429.8	TSL:1	c.579C>G	p.Ser193Ser	synonymous	Exon 7 of 35	ENSP00000317997.4	Q9NRD9-1
	DUOX1	ENST00000885347.1		c.579C>G	p.Ser193Ser	synonymous	Exon 5 of 33	ENSP00000555406.1

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 1043 AN: 151934 Hom.: 6 Cov.: 31

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

GnomAD2 exomes AF: 0.00464 AC: 743 AN: 160266 AF XY: 0.00456

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 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.: 34 AF XY: 0.00949 AC XY: 6584 AN XY: 693932

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00143 AC: 46 AN: 32226

American (AMR) AF: 0.00367 AC: 136 AN: 37068

Ashkenazi Jewish (ASJ) AF: 0.000555 AC: 14 AN: 25240

East Asian (EAS) AF: 0.000245 AC: 9 AN: 36784

South Asian (SAS) AF: 0.00134 AC: 107 AN: 80082

European-Finnish (FIN) AF: 0.00785 AC: 379 AN: 48268

Middle Eastern (MID) AF: 0.00117 AC: 5 AN: 4280

European-Non Finnish (NFE) AF: 0.0117 AC: 12670 AN: 1082090

Other (OTH) AF: 0.00831 AC: 483 AN: 58148

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00686 AC: 1043 AN: 152052 Hom.: 6 Cov.: 31 AF XY: 0.00632 AC XY: 470 AN XY: 74356

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00217 AC: 90 AN: 41388

American (AMR) AF: 0.00530 AC: 81 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00678 AC: 72 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 784 AN: 67952

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00728 Hom.: 3

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		-0.89
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs397834845; hg19: chr15-45427755;