rs1239567712

Variant summary

Our verdict is Uncertain significance. Variant got 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.

Frequency

Genomes: not found (cov: 34)

Consequence

NOXO1
NM_172167.3 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOXO1NM_172167.3 linkc.786G>T p.Leu262Phe missense_variant Exon 7 of 8 ENST00000356120.9 NP_751907.1 Q8NFA2-3A8K832
TBL3NM_006453.3 linkc.*772C>A 3_prime_UTR_variant Exon 22 of 22 ENST00000568546.6 NP_006444.2 Q12788

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOXO1ENST00000356120.9 linkc.786G>T p.Leu262Phe missense_variant Exon 7 of 8 1 NM_172167.3 ENSP00000348435.4 Q8NFA2-3
TBL3ENST00000568546.6 linkc.*772C>A 3_prime_UTR_variant Exon 22 of 22 1 NM_006453.3 ENSP00000454836.1 Q12788

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
M_CAP
Pathogenic
0.30
D
MetaRNN
Uncertain
0.71
D;D;D;D
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.5
.;.;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.5
D;D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0060
D;D;D;D
Sift4G
Uncertain
0.010
D;D;D;D
Polyphen
1.0
D;D;D;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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1239567712; hg19: chr16-2029458; API