chr12-98533444-C-T
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000266732.8(TMPO):c.1187C>T(p.Thr396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000266732.8 missense
Scores
Clinical Significance
Conservation
Publications
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
- dilated cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+1606C>T | intron_variant | Intron 3 of 8 | ENST00000556029.6 | NP_001027454.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251404 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727234 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Thr396Ile variant in the TMPO gene has not been previously reported in indiv iduals with cardiomyopathy and was absent from large population studies. Computa tional prediction tools and conservation analysis suggest that the Thr396Ile var iant may not impact the protein, though this information is not predictive enoug h to rule out pathogenicity. Additional studies are needed to fully assess the c linical significance of this variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at