6-18138997-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000367.5(TPMT):c.460G>A(p.Ala154Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,611,706 control chromosomes in the GnomAD database, including 1,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,other (★★).
Frequency
Consequence
NM_000367.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPMT | NM_000367.5 | c.460G>A | p.Ala154Thr | missense_variant | Exon 6 of 9 | ENST00000309983.5 | NP_000358.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0259 AC: 3936AN: 152194Hom.: 74 Cov.: 32
GnomAD3 exomes AF: 0.0280 AC: 7048AN: 251358Hom.: 160 AF XY: 0.0266 AC XY: 3619AN XY: 135858
GnomAD4 exome AF: 0.0361 AC: 52612AN: 1459394Hom.: 1188 Cov.: 34 AF XY: 0.0349 AC XY: 25355AN XY: 726138
GnomAD4 genome AF: 0.0258 AC: 3933AN: 152312Hom.: 73 Cov.: 32 AF XY: 0.0253 AC XY: 1887AN XY: 74482
ClinVar
Submissions by phenotype
not provided Benign:3Other:1
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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. -
- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).
TPMT: BS1, BS2 -
TPMT-related disorder Benign:1
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). -
Thiopurine S-methyltransferase deficiency Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at