12-98515857-A-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001032283.3(TMPO):c.-11A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,610,236 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
Consequence
NM_001032283.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.-11A>C | 5_prime_UTR_variant | Exon 1 of 9 | ENST00000556029.6 | NP_001027454.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000116 AC: 28AN: 242416Hom.: 0 AF XY: 0.000129 AC XY: 17AN XY: 131878
GnomAD4 exome AF: 0.000296 AC: 432AN: 1458044Hom.: 0 Cov.: 31 AF XY: 0.000291 AC XY: 211AN XY: 725126
GnomAD4 genome AF: 0.000177 AC: 27AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74352
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: TMPO c.-11A>C is located in the untranslated mRNA region upstream of the initiation codon. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00012 in 242416 control chromosomes, predominantly at a frequency of 0.00025 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 16 fold of the estimated maximal expected allele frequency for a pathogenic variant in TMPO causing Dilated Cardiomyopathy phenotype (1.6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.-11A>C in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with a pathogenic variant has been reported (MYH7 c.1063G>A, p.A355T), providing supporting evidence for a benign role. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at