chr7-144765897-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_022445.4(TPK1):c.98G>A(p.Arg33His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,611,206 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. R33C) has been classified as Uncertain significance.
Frequency
Consequence
NM_022445.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPK1 | NM_022445.4 | c.98G>A | p.Arg33His | missense_variant | 3/9 | ENST00000360057.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPK1 | ENST00000360057.7 | c.98G>A | p.Arg33His | missense_variant | 3/9 | 1 | NM_022445.4 | P1 | |
TPK1 | ENST00000378098.8 | c.98G>A | p.Arg33His | missense_variant, NMD_transcript_variant | 3/10 | 1 | |||
TPK1 | ENST00000378099.7 | c.98G>A | p.Arg33His | missense_variant | 3/8 | 3 | |||
TPK1 | ENST00000552881.1 | c.98G>A | p.Arg33His | missense_variant | 3/7 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00517 AC: 786AN: 151930Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00512 AC: 1272AN: 248596Hom.: 6 AF XY: 0.00501 AC XY: 673AN XY: 134340
GnomAD4 exome AF: 0.00794 AC: 11589AN: 1459158Hom.: 67 Cov.: 31 AF XY: 0.00767 AC XY: 5570AN XY: 725832
GnomAD4 genome ? AF: 0.00517 AC: 786AN: 152048Hom.: 6 Cov.: 32 AF XY: 0.00491 AC XY: 365AN XY: 74322
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TPK1: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Dec 13, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 13, 2017 | - - |
Childhood encephalopathy due to thiamine pyrophosphokinase deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 03, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
TPK1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 20, 2023 | This variant is classified as 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