rs749378489

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172167.3(NOXO1):ā€‹c.712T>Gā€‹(p.Cys238Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,804 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

NOXO1
NM_172167.3 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26
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 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.712T>G p.Cys238Gly missense_variant Exon 7 of 8 ENST00000356120.9 NP_751907.1 Q8NFA2-3A8K832
TBL3NM_006453.3 linkc.*846A>C 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.712T>G p.Cys238Gly missense_variant Exon 7 of 8 1 NM_172167.3 ENSP00000348435.4 Q8NFA2-3
TBL3ENST00000568546.6 linkc.*846A>C 3_prime_UTR_variant Exon 22 of 22 1 NM_006453.3 ENSP00000454836.1 Q12788

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000409
AC:
1
AN:
244594
Hom.:
0
AF XY:
0.00000750
AC XY:
1
AN XY:
133300
show subpopulations
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 SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457804
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
724882
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
ExAC
AF:
0.00000829
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Benign
0.91
DEOGEN2
Benign
0.41
.;.;T;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.69
T;T;T;T
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Benign
-0.85
T
MutationAssessor
Pathogenic
3.0
.;.;M;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-6.1
D;D;D;D
REVEL
Benign
0.25
Sift
Benign
0.034
D;D;D;D
Sift4G
Uncertain
0.041
D;D;D;D
Polyphen
0.99
D;D;D;D
Vest4
0.50
MutPred
0.49
.;.;Gain of glycosylation at S245 (P = 0.0666);.;
MVP
0.35
MPC
0.81
ClinPred
0.45
T
GERP RS
5.1
Varity_R
0.60
gMVP
0.71

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: rs749378489; hg19: chr16-2029532; API