chr9-137428997-C-T

Variant names:

• chr9-137428997-C-T
• rs1564237794
• NM_001256067.2:c.485C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256067.2(NOXA1):​c.485C>T​(p.Ser162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 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: 7.0e-7 (0 hom.)
• Consequence: NOXA1 NM_001256067.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.558
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046517164).

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.485C>T	p.Ser162Leu	missense	Exon 4 of 14	NP_001242996.1	Q86UR1-1
	NOXA1	NM_006647.2		c.485C>T	p.Ser162Leu	missense	Exon 4 of 14	NP_006638.1	Q86UR1-2
	NOXA1	NM_001256068.2		c.485C>T	p.Ser162Leu	missense	Exon 4 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.485C>T	p.Ser162Leu	missense	Exon 4 of 14	ENSP00000507846.1	Q86UR1-1
	NOXA1	ENST00000341349.6	TSL:1	c.485C>T	p.Ser162Leu	missense	Exon 4 of 14	ENSP00000342848.2	Q86UR1-2
	NOXA1	ENST00000392815.2	TSL:1	c.485C>T	p.Ser162Leu	missense	Exon 4 of 12	ENSP00000376562.2	Q86UR1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215388 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: 0.0000584

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422262 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 702492

African (AFR) AF: 0.00 AC: 0 AN: 32530

American (AMR) AF: 0.00 AC: 0 AN: 39962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24318

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38772

South Asian (SAS) AF: 0.00 AC: 0 AN: 81096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090500

Other (OTH) AF: 0.00 AC: 0 AN: 58554

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	0.088
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.6
DANN	Benign	0.95
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.56
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.35	T
Sift4G	Benign	0.48	T
Polyphen		0.0060	B
Vest4		0.14
MutPred		0.38		Loss of disorder (P = 0.0272)
MVP		0.37
MPC		0.072
ClinPred		0.14	T
GERP RS		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
gMVP		0.26
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1564237794; hg19: chr9-140323449;