5-135029030-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002653.5(PITX1):c.694G>A(p.Gly232Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002653.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PITX1 | NM_002653.5 | c.694G>A | p.Gly232Ser | missense_variant | Exon 3 of 3 | ENST00000265340.12 | NP_002644.4 | |
PITX1 | XM_047417318.1 | c.796G>A | p.Gly266Ser | missense_variant | Exon 4 of 4 | XP_047273274.1 | ||
PITX1 | XM_047417319.1 | c.349G>A | p.Gly117Ser | missense_variant | Exon 3 of 3 | XP_047273275.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251394Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135910
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461870Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74386
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.694G>A (p.G232S) alteration is located in exon 3 (coding exon 3) of the PITX1 gene. This alteration results from a G to A substitution at nucleotide position 694, causing the glycine (G) at amino acid position 232 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 232 of the PITX1 protein (p.Gly232Ser). This variant is present in population databases (rs746291345, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with PITX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1406694). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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