rs12316677
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000266732.8(TMPO):c.1632T>A(p.Ile544=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,614,170 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I544I) has been classified as Likely benign.
Frequency
Consequence
ENST00000266732.8 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+2051T>A | intron_variant | ENST00000556029.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.565+2051T>A | intron_variant | 1 | NM_001032283.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0140 AC: 2130AN: 152198Hom.: 41 Cov.: 33
GnomAD3 exomes AF: 0.00350 AC: 879AN: 251270Hom.: 12 AF XY: 0.00254 AC XY: 345AN XY: 135818
GnomAD4 exome AF: 0.00130 AC: 1899AN: 1461854Hom.: 34 Cov.: 32 AF XY: 0.00112 AC XY: 812AN XY: 727220
GnomAD4 genome ? AF: 0.0140 AC: 2130AN: 152316Hom.: 41 Cov.: 33 AF XY: 0.0133 AC XY: 989AN XY: 74484
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 15, 2016 | This alteration is classified as 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. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Ile544Ile in Exon 04 of TMPO: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence and has been identified in 4.9% (183/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12316677). - |
Loeys-Dietz syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at