chr5-43615851-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_182977.3(NNT):c.385C>T(p.Arg129*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
NNT
NM_182977.3 stop_gained
NM_182977.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.53
Publications
2 publications found
Genes affected
NNT (HGNC:7863): (nicotinamide nucleotide transhydrogenase) This gene encodes an integral protein of the inner mitochondrial membrane. The enzyme couples hydride transfer between NAD(H) and NADP(+) to proton translocation across the inner mitochondrial membrane. Under most physiological conditions, the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH. The resulting NADPH is used for biosynthesis and in free radical detoxification. [provided by RefSeq, Sep 2016]
NNT Gene-Disease associations (from GenCC):
- glucocorticoid deficiency 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- familial glucocorticoid deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-43615851-C-T is Pathogenic according to our data. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-43615851-C-T is described in CliVar as Pathogenic. Clinvar id is 265843.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NNT | NM_182977.3 | c.385C>T | p.Arg129* | stop_gained | Exon 4 of 22 | ENST00000344920.9 | NP_892022.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000820 AC: 2AN: 243784 AF XY: 0.00000758 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
243784
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1451466Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 721436 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1451466
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
721436
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32956
American (AMR)
AF:
AC:
0
AN:
42958
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25764
East Asian (EAS)
AF:
AC:
0
AN:
39544
South Asian (SAS)
AF:
AC:
0
AN:
84124
European-Finnish (FIN)
AF:
AC:
2
AN:
53284
Middle Eastern (MID)
AF:
AC:
0
AN:
5648
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1107288
Other (OTH)
AF:
AC:
1
AN:
59900
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Glucocorticoid deficiency 4 Pathogenic:1
Oct 11, 2016
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
PhyloP100
Vest4
0.98
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
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