Genetic Variant NM_001256067.2:c.107C>T (chr9-137423636-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOXA1	NM_001256067.2 link	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14	ENST00000683555.1	NP_001242996.1	Q86UR1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOXA1	ENST00000683555.1 link	c.107C>T	p.Pro36Leu	missense_variant	Exon 1 of 14		NM_001256067.2	ENSP00000507846.1		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

GnomAD2 exomes

AF:

0.000211

AC:

AN:

89872

AF XY:

0.000210

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 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

African (AFR)

AF:

0.0000378

AC:

AN:

26452

American (AMR)

AF:

0.0000744

AC:

AN:

26886

Ashkenazi Jewish (ASJ)

AF:

0.00101

AC:

AN:

21852

East Asian (EAS)

AF:

0.00

AC:

AN:

27126

South Asian (SAS)

AF:

0.0000146

AC:

AN:

68320

European-Finnish (FIN)

AF:

0.000186

AC:

AN:

32300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4532

European-Non Finnish (NFE)

AF:

0.000131

AC:

134

AN:

1024994

Other (OTH)

AF:

0.000134

AC:

AN:

52118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000106

AC:

AN:

151614

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000964

AC:

AN:

10378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67842

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Aug 23, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

0.38

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

PromoterAI

0.039

Neutral

(source)

gMVP

0.42

Mutation Taster

=70/30

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.

NM_001256067.2:c.107C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over