11-18036028-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004179.3(TPH1):c.232C>T(p.His78Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000381 in 1,612,674 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 4 hom. )
Consequence
TPH1
NM_004179.3 missense
NM_004179.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 6.69
Publications
5 publications found
Genes affected
TPH1 (HGNC:12008): (tryptophan hydroxylase 1) This gene encodes a member of the aromatic amino acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009954572).
BP6
Variant 11-18036028-G-A is Benign according to our data. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-18036028-G-A is described in CliVar as Benign. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 152182Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
57
AN:
152182
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:
GnomAD2 exomes AF: 0.000748 AC: 188AN: 251222 AF XY: 0.000773 show subpopulations
GnomAD2 exomes
AF:
AC:
188
AN:
251222
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: 0.000381 AC: 557AN: 1460492Hom.: 4 Cov.: 30 AF XY: 0.000377 AC XY: 274AN XY: 726610 show subpopulations
GnomAD4 exome
AF:
AC:
557
AN:
1460492
Hom.:
Cov.:
30
AF XY:
AC XY:
274
AN XY:
726610
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33436
American (AMR)
AF:
AC:
6
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
393
AN:
26122
East Asian (EAS)
AF:
AC:
0
AN:
39632
South Asian (SAS)
AF:
AC:
1
AN:
86206
European-Finnish (FIN)
AF:
AC:
0
AN:
53324
Middle Eastern (MID)
AF:
AC:
0
AN:
5002
European-Non Finnish (NFE)
AF:
AC:
78
AN:
1111750
Other (OTH)
AF:
AC:
77
AN:
60298
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.461
Heterozygous variant carriers
0
30
60
90
120
150
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
20
40
60
80
100
<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 AF: 0.000375 AC: 57AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74332 show subpopulations
GnomAD4 genome
AF:
AC:
57
AN:
152182
Hom.:
Cov.:
32
AF XY:
AC XY:
29
AN XY:
74332
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41448
American (AMR)
AF:
AC:
3
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
44
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
7
AN:
68034
Other (OTH)
AF:
AC:
1
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome 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
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
9
ExAC
AF:
AC:
63
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Aug 22, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;.
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;.
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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
Publications
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