16-1979090-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_172167.3(NOXO1):ā€‹c.1078T>Gā€‹(p.Cys360Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 34)
Exomes š‘“: 0.0000081 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NOXO1
NM_172167.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.248
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 -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06773302).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOXO1NM_172167.3 linkc.1078T>G p.Cys360Gly missense_variant Exon 8 of 8 ENST00000356120.9 NP_751907.1 Q8NFA2-3A8K832
TBL3NM_006453.3 linkc.*405A>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.1078T>G p.Cys360Gly missense_variant Exon 8 of 8 1 NM_172167.3 ENSP00000348435.4 Q8NFA2-3
TBL3ENST00000568546.6 linkc.*405A>C 3_prime_UTR_variant Exon 22 of 22 1 NM_006453.3 ENSP00000454836.1 Q12788

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
151836
Hom.:
0
Cov.:
34
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000808
AC:
11
AN:
1361252
Hom.:
0
Cov.:
33
AF XY:
0.0000104
AC XY:
7
AN XY:
673676
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000368
Gnomad4 ASJ exome
AF:
0.0000421
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000590
Gnomad4 NFE exome
AF:
0.00000464
Gnomad4 OTH exome
AF:
0.0000353
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000659
AC:
1
AN:
151836
Hom.:
0
Cov.:
34
AF XY:
0.0000135
AC XY:
1
AN XY:
74160
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000930
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1093T>G (p.C365G) alteration is located in exon 8 (coding exon 8) of the NOXO1 gene. This alteration results from a T to G substitution at nucleotide position 1093, causing the cysteine (C) at amino acid position 365 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
6.1
DANN
Benign
0.60
DEOGEN2
Benign
0.039
.;.;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.099
N
LIST_S2
Benign
0.38
T;T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.068
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
.;.;L;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.40
N;N;N;N
REVEL
Benign
0.046
Sift
Benign
0.058
T;T;D;D
Sift4G
Benign
0.088
T;T;T;T
Polyphen
0.36
B;B;B;B
Vest4
0.082
MVP
0.22
MPC
0.33
ClinPred
0.039
T
GERP RS
-1.9
Varity_R
0.083
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs769723846; hg19: chr16-2029091; API