16-1979819-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_172167.3(NOXO1):ā€‹c.671G>Cā€‹(p.Arg224Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,565,724 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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: š‘“ 0.00026 ( 1 hom., cov: 34)
Exomes š‘“: 0.00013 ( 3 hom. )

Consequence

NOXO1
NM_172167.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0037693381).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOXO1NM_172167.3 linkc.671G>C p.Arg224Pro missense_variant Exon 6 of 8 ENST00000356120.9 NP_751907.1 Q8NFA2-3A8K832
TBL3NM_006453.3 linkc.*1134C>G 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.671G>C p.Arg224Pro missense_variant Exon 6 of 8 1 NM_172167.3 ENSP00000348435.4 Q8NFA2-3
TBL3ENST00000568546.6 linkc.*1134C>G 3_prime_UTR_variant Exon 22 of 22 1 NM_006453.3 ENSP00000454836.1 Q12788

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152280
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00673
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000518
AC:
91
AN:
175792
Hom.:
1
AF XY:
0.000472
AC XY:
45
AN XY:
95302
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00661
Gnomad SAS exome
AF:
0.0000809
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000137
Gnomad OTH exome
AF:
0.000644
GnomAD4 exome
AF:
0.000134
AC:
190
AN:
1413326
Hom.:
3
Cov.:
32
AF XY:
0.000132
AC XY:
92
AN XY:
699432
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00397
Gnomad4 SAS exome
AF:
0.000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.000394
GnomAD4 genome
AF:
0.000262
AC:
40
AN:
152398
Hom.:
1
Cov.:
34
AF XY:
0.000295
AC XY:
22
AN XY:
74522
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00675
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000224
Hom.:
0
Bravo
AF:
0.000378
ExAC
AF:
0.000405
AC:
48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.11
DANN
Benign
0.70
DEOGEN2
Benign
0.090
.;.;T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.42
T;T;T;T
MetaRNN
Benign
0.0038
T;T;T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
0.76
.;.;N;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.87
N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.27
T;T;T;T
Sift4G
Benign
0.32
T;T;T;T
Polyphen
0.57
P;P;P;P
Vest4
0.085
MVP
0.41
MPC
0.38
ClinPred
0.038
T
GERP RS
-9.5
Varity_R
0.13
gMVP
0.40

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: rs192494277; hg19: chr16-2029820; API