11-18036028-G-A
Variant summary
Our verdict is Benign. Variant got -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
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 ClinVar as [Benign]. Clinvar id is 781809.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPH1 | NM_004179.3 | c.232C>T | p.His78Tyr | missense_variant | 3/11 | ENST00000682019.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPH1 | ENST00000682019.1 | c.232C>T | p.His78Tyr | missense_variant | 3/11 | NM_004179.3 | P1 | ||
TPH1 | ENST00000250018.6 | c.232C>T | p.His78Tyr | missense_variant | 2/10 | 1 | P1 | ||
TPH1 | ENST00000417164.5 | c.232C>T | p.His78Tyr | missense_variant, NMD_transcript_variant | 2/9 | 1 | |||
TPH1 | ENST00000528338.1 | c.262C>T | p.His88Tyr | missense_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000375 AC: 57AN: 152182Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000748 AC: 188AN: 251222Hom.: 4 AF XY: 0.000773 AC XY: 105AN XY: 135816
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GnomAD4 exome AF: 0.000381 AC: 557AN: 1460492Hom.: 4 Cov.: 30 AF XY: 0.000377 AC XY: 274AN XY: 726610
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GnomAD4 genome ? AF: 0.000375 AC: 57AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74332
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
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;.
MutationTaster
Benign
D;D
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
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at