16-1979457-C-A

Variant names:

• chr16-1979457-C-A
• rs1239567712
• NM_172167.3:c.786G>T

Variant summary

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

The NM_172167.3(NOXO1):​c.786G>T​(p.Leu262Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L262L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NOXO1 NM_172167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 0 publications found

Genes affected

NOXO1 (HGNC:19404): (NADPH oxidase organizer 1) This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

TBL3 (HGNC:11587): (transducin beta like 3) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This gene has multiple polyadenylation sites. It might have multiple alternatively spliced transcript variants but the variants have not been fully described yet. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172167.3. 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
	NOXO1	NM_172167.3	MANE Select	c.786G>T	p.Leu262Phe	missense	Exon 7 of 8	NP_751907.1	Q8NFA2-3
	TBL3	NM_006453.3	MANE Select	c.*772C>A		3_prime_UTR	Exon 22 of 22	NP_006444.2
	NOXO1	NM_172168.3		c.801G>T	p.Leu267Phe	missense	Exon 7 of 8	NP_751908.1	Q8NFA2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXO1	ENST00000356120.9	TSL:1 MANE Select	c.786G>T	p.Leu262Phe	missense	Exon 7 of 8	ENSP00000348435.4	Q8NFA2-3
	NOXO1	ENST00000397280.8	TSL:1	c.801G>T	p.Leu267Phe	missense	Exon 7 of 8	ENSP00000380450.4	Q8NFA2-1
	NOXO1	ENST00000566005.5	TSL:1	c.798G>T	p.Leu266Phe	missense	Exon 7 of 8	ENSP00000456800.1	Q8NFA2-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.033
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.68		Loss of MoRF binding (P = 0.1204)
MVP		0.69
MPC		0.98
ClinPred		0.69	D
GERP RS		1.6
Varity_R		0.26
gMVP		0.60

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: rs1239567712; hg19: chr16-2029458;