NM_172167.3:c.671G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_172167.3(NOXO1):c.671G>T(p.Arg224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,565,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R224W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

NOXO1
NM_172167.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.46

Publications

1 publications found

Variant links:

Genes affected

NOXO1 (HGNC:19404): (NADPH oxidase organizer 1) This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

NOXO1 links:

TBL3 (HGNC:11587): (transducin beta like 3) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This gene has multiple polyadenylation sites. It might have multiple alternatively spliced transcript variants but the variants have not been fully described yet. [provided by RefSeq, Jul 2008]

TBL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06356913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172167.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXO1	NM_172167.3	MANE Select	c.671G>T	p.Arg224Leu	missense	Exon 6 of 8	NP_751907.1	Q8NFA2-3
TBL3	NM_006453.3	MANE Select	c.*1134C>A		3_prime_UTR	Exon 22 of 22	NP_006444.2
NOXO1	NM_172168.3		c.686G>T	p.Arg229Leu	missense	Exon 6 of 8	NP_751908.1	Q8NFA2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXO1	ENST00000356120.9	TSL:1 MANE Select	c.671G>T	p.Arg224Leu	missense	Exon 6 of 8	ENSP00000348435.4	Q8NFA2-3
NOXO1	ENST00000397280.8	TSL:1	c.686G>T	p.Arg229Leu	missense	Exon 6 of 8	ENSP00000380450.4	Q8NFA2-1
NOXO1	ENST00000566005.5	TSL:1	c.683G>T	p.Arg228Leu	missense	Exon 6 of 8	ENSP00000456800.1	Q8NFA2-2

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

152280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000455

AC:

AN:

175792

AF XY:

0.0000420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000109

AC:

154

AN:

1413326

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

699432

show subpopulations

African (AFR)

AF:

0.000155

AC:

AN:

32176

American (AMR)

AF:

0.0000260

AC:

AN:

38504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25340

East Asian (EAS)

AF:

0.00

AC:

AN:

36804

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47228

Middle Eastern (MID)

AF:

0.00231

AC:

AN:

4752

European-Non Finnish (NFE)

AF:

0.000117

AC:

127

AN:

1089044

Other (OTH)

AF:

0.000154

AC:

AN:

58414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152398

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41602

American (AMR)

AF:

0.000261

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000169

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.031

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.16

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.55

M_CAP

Benign

0.029

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

PhyloP100

-2.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.35

Sift4G

Benign

0.52

Polyphen

0.12

Vest4

0.22

MVP

0.41

MPC

0.35

ClinPred

0.078

GERP RS

-9.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.052

gMVP

0.37

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over