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GeneBe

9-137429324-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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 (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

NOXA1
NM_001256067.2 missense

Scores

3
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOXA1NM_001256067.2 linkuse as main transcriptc.553C>T p.Arg185Trp missense_variant 5/14 ENST00000683555.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOXA1ENST00000683555.1 linkuse as main transcriptc.553C>T p.Arg185Trp missense_variant 5/14 NM_001256067.2 P1Q86UR1-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152198
Hom.:
0
Cov.:
33
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
GnomAD3 exomes
AF:
0.0000409
AC:
8
AN:
195742
Hom.:
0
AF XY:
0.0000285
AC XY:
3
AN XY:
105384
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 SAS exome
AF:
0.000119
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000586
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
42
AN:
1428656
Hom.:
0
Cov.:
31
AF XY:
0.0000311
AC XY:
22
AN XY:
707390
show subpopulations
Gnomad4 AFR exome
AF:
0.0000604
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000261
Gnomad4 SAS exome
AF:
0.0000982
Gnomad4 FIN exome
AF:
0.0000202
Gnomad4 NFE exome
AF:
0.0000182
Gnomad4 OTH exome
AF:
0.000101
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000774
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000422
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 18, 2023The c.553C>T (p.R185W) alteration is located in exon 5 (coding exon 5) of the NOXA1 gene. This alteration results from a C to T substitution at nucleotide position 553, causing the arginine (R) at amino acid position 185 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
Cadd
Uncertain
25
Dann
Uncertain
1.0
Eigen
Uncertain
0.31
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.34
D
MetaRNN
Uncertain
0.70
D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.87
D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-6.5
D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.012
D
Polyphen
1.0
D
Vest4
0.55
MVP
0.75
MPC
0.44
ClinPred
0.95
D
GERP RS
0.91
gMVP
0.74

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755916333; hg19: chr9-140323776; API