9-137431253-C-A

Position:

• chr9-137431253-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256067.2(NOXA1):​c.716C>A​(p.Ser239Tyr) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: NOXA1 NM_001256067.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.862

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

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=0.1438106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOXA1	NM_001256067.2	c.716C>A	p.Ser239Tyr	missense_variant	8/14	ENST00000683555.1	NP_001242996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOXA1	ENST00000683555.1	c.716C>A	p.Ser239Tyr	missense_variant	8/14		NM_001256067.2	ENSP00000507846	P1
NOXA1	ENST00000341349.6	c.716C>A	p.Ser239Tyr	missense_variant	8/14	1		ENSP00000342848
NOXA1	ENST00000392815.2	c.548C>A	p.Ser183Tyr	missense_variant	6/12	1		ENSP00000376562
NOXA1	ENST00000683683.1	c.590C>A	p.Ser197Tyr	missense_variant	7/9			ENSP00000506984

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.716C>A (p.S239Y) alteration is located in exon 8 (coding exon 8) of the NOXA1 gene. This alteration results from a C to A substitution at nucleotide position 716, causing the serine (S) at amino acid position 239 to be replaced by a tyrosine (Y). 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	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	1.8
DANN	Benign	0.81
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.020	D;T
Sift4G	Benign	1.0	T;T
Polyphen		0.92	P;D
Vest4		0.22
MutPred		0.26		Gain of helix (P = 0.0078);.;
MVP		0.59
MPC		0.12
ClinPred		0.12	T
GERP RS		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140325705;