9-137429360-G-T

Variant names:

• chr9-137429360-G-T
• rs879073978
• NM_001256067.2:c.589G>T

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.589G>T​(p.Val197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V197M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOXA1 NM_001256067.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• 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=0.07189223).

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.589G>T	p.Val197Leu	missense	Exon 5 of 14	NP_001242996.1	Q86UR1-1
	NOXA1	NM_006647.2		c.589G>T	p.Val197Leu	missense	Exon 5 of 14	NP_006638.1	Q86UR1-2
	NOXA1	NM_001256068.2		c.504+344G>T		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.589G>T	p.Val197Leu	missense	Exon 5 of 14	ENSP00000507846.1	Q86UR1-1
	NOXA1	ENST00000341349.6	TSL:1	c.589G>T	p.Val197Leu	missense	Exon 5 of 14	ENSP00000342848.2	Q86UR1-2
	NOXA1	ENST00000392815.2	TSL:1	c.504+344G>T		intron	N/A	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1429996 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708210

African (AFR) AF: 0.00 AC: 0 AN: 33142

American (AMR) AF: 0.00 AC: 0 AN: 39376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25320

East Asian (EAS) AF: 0.00 AC: 0 AN: 38562

South Asian (SAS) AF: 0.00 AC: 0 AN: 81514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097206

Other (OTH) AF: 0.00 AC: 0 AN: 59282

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.17
DANN	Benign	0.93
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.61
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.086
Sift	Benign	0.39	T
Sift4G	Benign	0.20	T
Polyphen		0.081	B
Vest4		0.14
MutPred		0.33		Gain of helix (P = 0.027)
MVP		0.53
MPC		0.13
ClinPred		0.23	T
GERP RS		0.78
gMVP		0.32
Mutation Taster		=96/4	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: rs879073978; hg19: chr9-140323812;