Genetic Variant NOXA1:p.Arg185Trp (chr9-137429324-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001256067.2(NOXA1):c.553C>T(p.Arg185Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,580,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R185Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

NOXA1
NM_001256067.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270

Publications

1 publications found

Variant links:

Genes affected

NOXA1 (HGNC:10668): (NADPH oxidase activator 1) This gene encodes a protein which activates NADPH oxidases, enzymes which catalyze a reaction generating reactive oxygen species. The encoded protein contains four N-terminal tetratricopeptide domains and a C-terminal Src homology 3 domain. Interaction between the encoded protein and proteins in the oxidase regulatory complex occur via the tetratricopeptide domains. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

NOXA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256067.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXA1	NM_001256067.2	MANE Select	c.553C>T	p.Arg185Trp	missense	Exon 5 of 14	NP_001242996.1	Q86UR1-1
NOXA1	NM_006647.2		c.553C>T	p.Arg185Trp	missense	Exon 5 of 14	NP_006638.1	Q86UR1-2
NOXA1	NM_001256068.2		c.504+308C>T		intron	N/A	NP_001242997.1	Q86UR1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXA1	ENST00000683555.1	MANE Select	c.553C>T	p.Arg185Trp	missense	Exon 5 of 14	ENSP00000507846.1	Q86UR1-1
NOXA1	ENST00000341349.6	TSL:1	c.553C>T	p.Arg185Trp	missense	Exon 5 of 14	ENSP00000342848.2	Q86UR1-2
NOXA1	ENST00000392815.2	TSL:1	c.504+308C>T		intron	N/A	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000409

AC:

AN:

195742

AF XY:

0.0000285

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:

0.0000586

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1428656

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

707390

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33094

American (AMR)

AF:

0.00

AC:

AN:

39092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25324

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38376

South Asian (SAS)

AF:

0.0000982

AC:

AN:

81442

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49508

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

1096914

Other (OTH)

AF:

0.000101

AC:

AN:

59206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

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:

0.0000526

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41440

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.0000774

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000422

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

0.17

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

-0.17

MutationAssessor

Pathogenic

3.1

PhyloP100

0.27

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.47

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.55

MVP

0.75

MPC

0.44

ClinPred

0.95

GERP RS

0.91

gMVP

0.74

Mutation Taster

=67/33

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