Genetic Variant NOXA1:p.Pro34Gln (chr9-137423630-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256067.2(NOXA1):c.101C>A(p.Pro34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000774 in 1,291,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P34L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

NOXA1
NM_001256067.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.426

Publications

0 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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13561088).

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.101C>A	p.Pro34Gln	missense	Exon 1 of 14	NP_001242996.1	Q86UR1-1
NOXA1	NM_006647.2		c.101C>A	p.Pro34Gln	missense	Exon 1 of 14	NP_006638.1	Q86UR1-2
NOXA1	NM_001256068.2		c.101C>A	p.Pro34Gln	missense	Exon 1 of 12	NP_001242997.1	Q86UR1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXA1	ENST00000683555.1	MANE Select	c.101C>A	p.Pro34Gln	missense	Exon 1 of 14	ENSP00000507846.1	Q86UR1-1
NOXA1	ENST00000341349.6	TSL:1	c.101C>A	p.Pro34Gln	missense	Exon 1 of 14	ENSP00000342848.2	Q86UR1-2
NOXA1	ENST00000392815.2	TSL:1	c.101C>A	p.Pro34Gln	missense	Exon 1 of 12	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.74e-7

AC:

AN:

1291704

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

638726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26544

American (AMR)

AF:

0.00

AC:

AN:

27396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21954

East Asian (EAS)

AF:

0.00

AC:

AN:

27316

South Asian (SAS)

AF:

0.00

AC:

AN:

69482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4584

European-Non Finnish (NFE)

AF:

9.71e-7

AC:

AN:

1029404

Other (OTH)

AF:

0.00

AC:

AN:

52428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.92

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.54

PhyloP100

-0.43

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.38

REVEL

Benign

0.078

Sift

Benign

0.48

Sift4G

Benign

0.38

Polyphen

0.93

Vest4

0.23

MutPred

0.38

Gain of solvent accessibility (P = 0.0365)

MVP

0.23

MPC

1.5

ClinPred

0.29

GERP RS

0.48

PromoterAI

-0.028

Neutral

(source)

gMVP

0.049

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over