rs1423582575

Variant names:

• chr9-137429318-G-A
• rs1423582575
• NM_001256067.2:c.547G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256067.2(NOXA1):​c.547G>A​(p.Val183Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V183G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NOXA1 NM_001256067.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.560
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2240763).

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.547G>A	p.Val183Ile	missense	Exon 5 of 14	NP_001242996.1	Q86UR1-1
	NOXA1	NM_006647.2		c.547G>A	p.Val183Ile	missense	Exon 5 of 14	NP_006638.1	Q86UR1-2
	NOXA1	NM_001256068.2		c.504+302G>A		intron	N/A	NP_001242997.1	Q86UR1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXA1	ENST00000683555.1	MANE Select	c.547G>A	p.Val183Ile	missense	Exon 5 of 14	ENSP00000507846.1	Q86UR1-1
	NOXA1	ENST00000341349.6	TSL:1	c.547G>A	p.Val183Ile	missense	Exon 5 of 14	ENSP00000342848.2	Q86UR1-2
	NOXA1	ENST00000392815.2	TSL:1	c.504+302G>A		intron	N/A	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000521 AC: 1 AN: 191782 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000121

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1426528 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 706130

African (AFR) AF: 0.00 AC: 0 AN: 33032

American (AMR) AF: 0.00 AC: 0 AN: 38732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25296

East Asian (EAS) AF: 0.00 AC: 0 AN: 38264

South Asian (SAS) AF: 0.00 AC: 0 AN: 81298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1095716

Other (OTH) AF: 0.00 AC: 0 AN: 59080

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.56
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.15
Sift	Benign	0.077	T
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.17
MutPred		0.29		Gain of helix (P = 0.0496)
MVP		0.52
MPC		0.40
ClinPred		0.28	T
GERP RS		2.2
gMVP		0.17
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1423582575; hg19: chr9-140323770;