chr16-69710994-C-G
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000903.3(NQO1):c.807G>C(p.Gln269His) variant causes a missense change. The variant allele was found at a frequency of 0.000903 in 1,612,638 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 6 hom. )
Consequence
NQO1
NM_000903.3 missense
NM_000903.3 missense
Scores
5
3
8
Clinical Significance
Conservation
PhyloP100: 4.63
Genes affected
NQO1 (HGNC:2874): (NAD(P)H quinone dehydrogenase 1) This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006585449).
BP6
?
Variant 16-69710994-C-G is Benign according to our data. Variant chr16-69710994-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 780185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NQO1 | NM_000903.3 | c.807G>C | p.Gln269His | missense_variant | 6/6 | ENST00000320623.10 | |
NQO1 | NM_001025433.2 | c.705G>C | p.Gln235His | missense_variant | 5/5 | ||
NQO1 | NM_001025434.2 | c.693G>C | p.Gln231His | missense_variant | 5/5 | ||
NQO1 | NM_001286137.2 | c.591G>C | p.Gln197His | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NQO1 | ENST00000320623.10 | c.807G>C | p.Gln269His | missense_variant | 6/6 | 1 | NM_000903.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00385 AC: 586AN: 152186Hom.: 4 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
586
AN:
152186
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00107 AC: 269AN: 250676Hom.: 2 AF XY: 0.000841 AC XY: 114AN XY: 135506
GnomAD3 exomes
AF:
AC:
269
AN:
250676
Hom.:
AF XY:
AC XY:
114
AN XY:
135506
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000596 AC: 871AN: 1460334Hom.: 6 Cov.: 31 AF XY: 0.000540 AC XY: 392AN XY: 726376
GnomAD4 exome
AF:
AC:
871
AN:
1460334
Hom.:
Cov.:
31
AF XY:
AC XY:
392
AN XY:
726376
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00384 AC: 585AN: 152304Hom.: 4 Cov.: 32 AF XY: 0.00344 AC XY: 256AN XY: 74474
GnomAD4 genome
?
AF:
AC:
585
AN:
152304
Hom.:
Cov.:
32
AF XY:
AC XY:
256
AN XY:
74474
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
54
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
169
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 26, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0, 1.0
.;D;.;D;.
Vest4
MutPred
0.069
.;Loss of helix (P = 0.0626);.;.;.;
MVP
MPC
1.1
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at