10-102230682-C-CGCG
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BS1_SupportingBS2
The NM_005029.4(PITX3):c.738_740dupCGC(p.Ala247dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.000537 in 1,578,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005029.4 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PITX3 | NM_005029.4 | c.738_740dupCGC | p.Ala247dup | disruptive_inframe_insertion | Exon 4 of 4 | ENST00000370002.8 | NP_005020.1 | |
PITX3 | XM_047425352.1 | c.738_740dupCGC | p.Ala247dup | disruptive_inframe_insertion | Exon 3 of 3 | XP_047281308.1 | ||
GBF1 | NM_001391923.1 | c.-230_-228dupGGC | 5_prime_UTR_variant | Exon 1 of 40 | NP_001378852.1 | |||
GBF1 | NM_001391924.1 | c.-368_-366dupGGC | 5_prime_UTR_variant | Exon 1 of 41 | NP_001378853.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152100Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000256 AC: 45AN: 175826Hom.: 0 AF XY: 0.000230 AC XY: 22AN XY: 95526
GnomAD4 exome AF: 0.000568 AC: 810AN: 1426408Hom.: 0 Cov.: 32 AF XY: 0.000536 AC XY: 379AN XY: 706706
GnomAD4 genome AF: 0.000243 AC: 37AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74430
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant, c.738_740dup, results in the insertion of 1 amino acid(s) of the PITX3 protein (p.Ala250dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs775510715, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PITX3-related conditions. ClinVar contains an entry for this variant (Variation ID: 665913). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at