11-18040669-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004179.3(TPH1):c.94A>G(p.Ile32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004179.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPH1 | NM_004179.3 | c.94A>G | p.Ile32Val | missense_variant | 2/11 | ENST00000682019.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPH1 | ENST00000682019.1 | c.94A>G | p.Ile32Val | missense_variant | 2/11 | NM_004179.3 | P1 | ||
TPH1 | ENST00000250018.6 | c.94A>G | p.Ile32Val | missense_variant | 1/10 | 1 | P1 | ||
TPH1 | ENST00000417164.5 | c.94A>G | p.Ile32Val | missense_variant, NMD_transcript_variant | 1/9 | 1 | |||
TPH1 | ENST00000528338.1 | c.124A>G | p.Ile42Val | missense_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248912Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134620
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459930Hom.: 0 Cov.: 30 AF XY: 0.0000262 AC XY: 19AN XY: 726216
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74480
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2021 | The c.94A>G (p.I32V) alteration is located in exon 1 (coding exon 1) of the TPH1 gene. This alteration results from a A to G substitution at nucleotide position 94, causing the isoleucine (I) at amino acid position 32 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at