NM_001256067.2:c.160C>T

Variant names:

• chr9-137423689-C-T
• rs1199557894
• NM_001256067.2:c.160C>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.160C>T​(p.Pro54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,181,974 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: NOXA1 NM_001256067.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.602
• 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=0.13726634).

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.160C>T	p.Pro54Ser	missense	Exon 1 of 14	NP_001242996.1	Q86UR1-1
	NOXA1	NM_006647.2		c.160C>T	p.Pro54Ser	missense	Exon 1 of 14	NP_006638.1	Q86UR1-2
	NOXA1	NM_001256068.2		c.160C>T	p.Pro54Ser	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.160C>T	p.Pro54Ser	missense	Exon 1 of 14	ENSP00000507846.1	Q86UR1-1
	NOXA1	ENST00000341349.6	TSL:1	c.160C>T	p.Pro54Ser	missense	Exon 1 of 14	ENSP00000342848.2	Q86UR1-2
	NOXA1	ENST00000392815.2	TSL:1	c.160C>T	p.Pro54Ser	missense	Exon 1 of 12	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000378 AC: 1 AN: 26478 AF XY: 0.0000603

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: 0.0000935

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1181974 Hom.: 0 Cov.: 31 AF XY: 0.00000173 AC XY: 1 AN XY: 577388

African (AFR) AF: 0.00 AC: 0 AN: 23800

American (AMR) AF: 0.00 AC: 0 AN: 13272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16870

East Asian (EAS) AF: 0.00 AC: 0 AN: 25784

South Asian (SAS) AF: 0.00 AC: 0 AN: 48874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3424

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 975044

Other (OTH) AF: 0.00 AC: 0 AN: 47272

GnomAD4 genome Cov.: 33

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	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.97
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.60
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.23
Sift	Benign	0.090	T
Sift4G	Benign	0.30	T
Polyphen		0.050	B
Vest4		0.22
MutPred		0.41		Gain of disorder (P = 0.2048)
MVP		0.25
MPC		1.7
ClinPred		0.065	T
GERP RS		2.5
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.21
Mutation Taster		=88/12	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: rs1199557894; hg19: chr9-140318141;