Variant 9-137423636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256067.2(NOXA1):c.107C>T(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,436,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

NOXA1
NM_001256067.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.380

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09348592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOXA1	NM_001256067.2 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	1/14	ENST00000683555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOXA1	ENST00000683555.1 linkuse as main transcript	c.107C>T	p.Pro36Leu	missense_variant	1/14		NM_001256067.2	P1	Q86UR1-1

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000964

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

89872

Hom.:

AF XY:

0.000210

AC XY:

AN XY:

52276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000618

Gnomad ASJ exome

AF:

0.000589

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000344

Gnomad NFE exome

AF:

0.000333

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

173

AN:

1284580

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

634882

show subpopulations

Gnomad4 AFR exome

AF:

0.0000378

Gnomad4 AMR exome

AF:

0.0000744

Gnomad4 ASJ exome

AF:

0.00101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000146

Gnomad4 FIN exome

AF:

0.000186

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000106

AC:

AN:

151614

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74022

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000964

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000929

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000125

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.107C>T (p.P36L) alteration is located in exon 1 (coding exon 1) of the NOXA1 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). 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

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.73

T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

0.66

D;N

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Benign

0.082

Sift

Benign

0.076

T;T

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.39

B;D

Vest4

0.21

MutPred

0.42

Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);

MVP

0.31

MPC

2.3

ClinPred

0.28

GERP RS

0.18

gMVP

0.42

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over