rs778613708
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000360.4(TH):c.685A>T(p.Ile229Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000569 in 1,562,782 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I229L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000360.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TH | NM_000360.4 | c.685A>T | p.Ile229Phe | missense_variant | 6/13 | ENST00000352909.8 | |
TH | NM_199292.3 | c.778A>T | p.Ile260Phe | missense_variant | 7/14 | ||
TH | NM_199293.3 | c.766A>T | p.Ile256Phe | missense_variant | 7/14 | ||
TH | XM_011520335.3 | c.697A>T | p.Ile233Phe | missense_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TH | ENST00000352909.8 | c.685A>T | p.Ile229Phe | missense_variant | 6/13 | 1 | NM_000360.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151976Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000397 AC: 69AN: 173642Hom.: 1 AF XY: 0.000238 AC XY: 22AN XY: 92352
GnomAD4 exome AF: 0.0000553 AC: 78AN: 1410806Hom.: 2 Cov.: 33 AF XY: 0.0000359 AC XY: 25AN XY: 696974
GnomAD4 genome ? AF: 0.0000724 AC: 11AN: 151976Hom.: 0 Cov.: 33 AF XY: 0.0000674 AC XY: 5AN XY: 74224
ClinVar
Submissions by phenotype
Autosomal recessive DOPA responsive dystonia Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
TH-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 12, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at