chr11-18022863-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_004179.3(TPH1):c.1095T>C(p.Leu365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 1,613,620 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0062 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0067 ( 35 hom. )
Consequence
TPH1
NM_004179.3 synonymous
NM_004179.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.47
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 11-18022863-A-G is Benign according to our data. Variant chr11-18022863-A-G is described in ClinVar as [Benign]. Clinvar id is 774690.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.47 with no splicing effect.
BS2
?
High Homozygotes in GnomAd at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPH1 | NM_004179.3 | c.1095T>C | p.Leu365= | synonymous_variant | 10/11 | ENST00000682019.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPH1 | ENST00000682019.1 | c.1095T>C | p.Leu365= | synonymous_variant | 10/11 | NM_004179.3 | P1 | ||
TPH1 | ENST00000250018.6 | c.1095T>C | p.Leu365= | synonymous_variant | 9/10 | 1 | P1 | ||
TPH1 | ENST00000417164.5 | c.*277T>C | 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 1 | ||||
TPH1 | ENST00000525406.1 | n.307T>C | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00625 AC: 951AN: 152186Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00604 AC: 1516AN: 251038Hom.: 10 AF XY: 0.00590 AC XY: 801AN XY: 135666
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GnomAD4 exome AF: 0.00672 AC: 9820AN: 1461316Hom.: 35 Cov.: 31 AF XY: 0.00652 AC XY: 4737AN XY: 726960
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GnomAD4 genome ? AF: 0.00624 AC: 951AN: 152304Hom.: 8 Cov.: 32 AF XY: 0.00616 AC XY: 459AN XY: 74476
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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 | Jul 13, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at