chr5-135033724-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002653.5(PITX1):c.158C>T(p.Thr53Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000094 in 1,596,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PITX1 | NM_002653.5 | c.158C>T | p.Thr53Met | missense_variant | Exon 1 of 3 | ENST00000265340.12 | NP_002644.4 | |
PITX1 | XM_047417318.1 | c.260C>T | p.Thr87Met | missense_variant | Exon 2 of 4 | XP_047273274.1 | ||
PITX1-AS1 | NR_161235.1 | n.267+184G>A | intron_variant | Intron 1 of 5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152104Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000457 AC: 10AN: 219016Hom.: 0 AF XY: 0.0000327 AC XY: 4AN XY: 122354
GnomAD4 exome AF: 0.00000900 AC: 13AN: 1444140Hom.: 0 Cov.: 31 AF XY: 0.00000556 AC XY: 4AN XY: 718888
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152104Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74292
ClinVar
Submissions by phenotype
Clubfoot Uncertain:1
The inherited heterozygous c.158C>T (p.Thr53Met) missense variant identified in the PITX1 gene has not been reported in affected individuals in the literature. The variant has 0.00001315 allele frequency in the gnomAD (v3) database (2 out of 152104 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. This variant has not been reported in the ClinVar database. This variant affects an evolutionarily conserved threonine residue [Thr53]. In silico tools provide conflicting predictions about potential pathogenicity of this variant (CADD score =26.2, REVEL score = 0.404). Due to the lack of compelling evidence for its pathogenicity, the heterozygous c.158C>T (p.Thr53Met) missense variant identified in the PITX1 gene is reported as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at