NM_001256067.2:c.107C>T

Variant names:

• chr9-137423636-C-T
• rs769002081
• NM_001256067.2:c.107C>T

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. 12/21 in silico tools predict 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.380
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.09348592).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXA1	NM_001256067.2	MANE Select	c.107C>T	p.Pro36Leu	missense	Exon 1 of 14	NP_001242996.1	Q86UR1-1
	NOXA1	NM_006647.2		c.107C>T	p.Pro36Leu	missense	Exon 1 of 14	NP_006638.1	Q86UR1-2
	NOXA1	NM_001256068.2		c.107C>T	p.Pro36Leu	missense	Exon 1 of 12	NP_001242997.1	Q86UR1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXA1	ENST00000683555.1	MANE Select	c.107C>T	p.Pro36Leu	missense	Exon 1 of 14	ENSP00000507846.1	Q86UR1-1
	NOXA1	ENST00000341349.6	TSL:1	c.107C>T	p.Pro36Leu	missense	Exon 1 of 14	ENSP00000342848.2	Q86UR1-2
	NOXA1	ENST00000392815.2	TSL:1	c.107C>T	p.Pro36Leu	missense	Exon 1 of 12	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 151614 Hom.: 0 Cov.: 33

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: 19 AN: 89872 AF XY: 0.000210

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.: 0 Cov.: 31 AF XY: 0.000140 AC XY: 89 AN XY: 634882

African (AFR) AF: 0.0000378 AC: 1 AN: 26452

American (AMR) AF: 0.0000744 AC: 2 AN: 26886

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 22 AN: 21852

East Asian (EAS) AF: 0.00 AC: 0 AN: 27126

South Asian (SAS) AF: 0.0000146 AC: 1 AN: 68320

European-Finnish (FIN) AF: 0.000186 AC: 6 AN: 32300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4532

European-Non Finnish (NFE) AF: 0.000131 AC: 134 AN: 1024994

Other (OTH) AF: 0.000134 AC: 7 AN: 52118

GnomAD4 genome AF: 0.000106 AC: 16 AN: 151614 Hom.: 0 Cov.: 33 AF XY: 0.0000675 AC XY: 5 AN XY: 74022

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000964 AC: 1 AN: 10378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67842

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000929 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.000125 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.96
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.38
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.082
Sift	Benign	0.076	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.39	B
Vest4		0.21
MutPred		0.42		Gain of helix (P = 0.0128)
MVP		0.31
MPC		2.3
ClinPred		0.28	T
GERP RS		0.18
PromoterAI		0.039	Neutral
gMVP		0.42
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs769002081; hg19: chr9-140318088;