5-135033813-T-TGGC
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_002653.5(PITX1):c.66_68dupGCC(p.Pro23dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000457 in 1,553,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002653.5 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PITX1 | NM_002653.5 | c.66_68dupGCC | p.Pro23dup | disruptive_inframe_insertion | Exon 1 of 3 | ENST00000265340.12 | NP_002644.4 | |
PITX1 | XM_047417318.1 | c.168_170dupGCC | p.Pro57dup | disruptive_inframe_insertion | Exon 2 of 4 | XP_047273274.1 | ||
PITX1-AS1 | NR_161235.1 | n.267+286_267+288dupGGC | intron_variant | Intron 1 of 5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000662 AC: 1AN: 151168Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000506 AC: 8AN: 158042Hom.: 0 AF XY: 0.0000559 AC XY: 5AN XY: 89438
GnomAD4 exome AF: 0.0000499 AC: 70AN: 1402382Hom.: 0 Cov.: 31 AF XY: 0.0000575 AC XY: 40AN XY: 695838
GnomAD4 genome AF: 0.00000662 AC: 1AN: 151168Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73764
ClinVar
Submissions by phenotype
PITX1-related disorder Uncertain:1
The PITX1 c.66_68dupGCC variant is predicted to result in an in-frame duplication (p.Pro24dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-134369503-T-TGGC). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This variant, c.66_68dup, results in the insertion of 1 amino acid(s) of the PITX1 protein (p.Pro24dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs776272532, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PITX1-related conditions. 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