chr7-144453638-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_022445.4(TPK1):c.639A>G(p.Thr213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TPK1
NM_022445.4 synonymous
NM_022445.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.55
Genes affected
TPK1 (HGNC:17358): (thiamin pyrophosphokinase 1) The protein encoded by this gene functions as a homodimer and catalyzes the conversion of thiamine to thiamine pyrophosphate, a cofactor for some enzymes of the glycolytic and energy production pathways. Defects in this gene are a cause of thiamine metabolism dysfunction syndrome-5. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 7-144453638-T-C is Benign according to our data. Variant chr7-144453638-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1158023.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-3.55 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPK1 | NM_022445.4 | c.639A>G | p.Thr213= | synonymous_variant | 9/9 | ENST00000360057.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPK1 | ENST00000360057.7 | c.639A>G | p.Thr213= | synonymous_variant | 9/9 | 1 | NM_022445.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251328Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135844
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461404Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727034
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GnomAD4 genome ? Cov.: 32
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Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Childhood encephalopathy due to thiamine pyrophosphokinase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at