rs761381643

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_172167.3(NOXO1):​c.1064G>T​(p.Gly355Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,345,510 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

NOXO1
NM_172167.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.060994506).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOXO1NM_172167.3 linkc.1064G>T p.Gly355Val missense_variant Exon 8 of 8 ENST00000356120.9 NP_751907.1 Q8NFA2-3A8K832
TBL3NM_006453.3 linkc.*419C>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.1064G>T p.Gly355Val missense_variant Exon 8 of 8 1 NM_172167.3 ENSP00000348435.4 Q8NFA2-3
TBL3ENST00000568546.6 linkc.*419C>A 3_prime_UTR_variant Exon 22 of 22 1 NM_006453.3 ENSP00000454836.1 Q12788

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000297
AC:
4
AN:
1345510
Hom.:
0
Cov.:
33
AF XY:
0.00000150
AC XY:
1
AN XY:
664966
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000373
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
9.2
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
.;.;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.43
T;T;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.061
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
.;.;L;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.2
N;N;N;N
REVEL
Benign
0.095
Sift
Uncertain
0.0080
D;D;D;D
Sift4G
Uncertain
0.025
D;D;D;D
Polyphen
0.017
B;B;B;B
Vest4
0.076
MutPred
0.21
.;.;Loss of relative solvent accessibility (P = 0.0186);.;
MVP
0.48
MPC
0.37
ClinPred
0.23
T
GERP RS
-5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.039
gMVP
0.18

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: chr16-2029105; API