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GeneBe

9-137423659-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001256067.2(NOXA1):c.130G>A(p.Ala44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000795 in 1,258,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

NOXA1
NM_001256067.2 missense

Scores

2
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.631
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33280522).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOXA1NM_001256067.2 linkuse as main transcriptc.130G>A p.Ala44Thr missense_variant 1/14 ENST00000683555.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOXA1ENST00000683555.1 linkuse as main transcriptc.130G>A p.Ala44Thr missense_variant 1/14 NM_001256067.2 P1Q86UR1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.95e-7
AC:
1
AN:
1258194
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
620442
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.89e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 GeneticsJan 29, 2024The c.130G>A (p.A44T) alteration is located in exon 1 (coding exon 1) of the NOXA1 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the alanine (A) at amino acid position 44 to be replaced by a threonine (T). 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
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
Cadd
Benign
16
Dann
Uncertain
0.98
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.74
T;T
M_CAP
Pathogenic
0.53
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.27
N;N
REVEL
Benign
0.14
Sift
Benign
0.10
T;T
Sift4G
Benign
0.098
T;T
Polyphen
0.045
B;P
Vest4
0.17
MutPred
0.45
Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP
0.50
MPC
1.2
ClinPred
0.11
T
GERP RS
-1.7
gMVP
0.098

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: rs1838677539; hg19: chr9-140318111; API