5-135028968-C-CG
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_002653.5(PITX1):c.755dupC(p.Leu253AlafsTer319) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002653.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PITX1 | NM_002653.5 | c.755dupC | p.Leu253AlafsTer319 | frameshift_variant | Exon 3 of 3 | ENST00000265340.12 | NP_002644.4 | |
PITX1 | XM_047417318.1 | c.857dupC | p.Leu287AlafsTer319 | frameshift_variant | Exon 4 of 4 | XP_047273274.1 | ||
PITX1 | XM_047417319.1 | c.410dupC | p.Leu138AlafsTer319 | frameshift_variant | Exon 3 of 3 | XP_047273275.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PITX1 | ENST00000265340.12 | c.755dupC | p.Leu253AlafsTer319 | frameshift_variant | Exon 3 of 3 | 1 | NM_002653.5 | ENSP00000265340.6 | ||
PITX1 | ENST00000506438.5 | c.755dupC | p.Leu253AlafsTer138 | frameshift_variant | Exon 4 of 4 | 1 | ENSP00000427542.1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with PITX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the PITX1 gene (p.Leu253Alafs*319). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 62 amino acid(s) of the PITX1 protein and extend the protein by 256 additional amino acid residues. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.