2-63054086-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014562.4(OTX1):c.137C>A(p.Thr46Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014562.4 missense
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 |
---|---|---|---|---|---|---|---|---|
OTX1 | NM_014562.4 | c.137C>A | p.Thr46Lys | missense_variant | Exon 4 of 5 | ENST00000282549.7 | NP_055377.1 | |
OTX1 | NM_001199770.2 | c.137C>A | p.Thr46Lys | missense_variant | Exon 4 of 5 | NP_001186699.1 | ||
OTX1 | NR_130153.2 | n.500C>A | non_coding_transcript_exon_variant | Exon 4 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTX1 | ENST00000282549.7 | c.137C>A | p.Thr46Lys | missense_variant | Exon 4 of 5 | 1 | NM_014562.4 | ENSP00000282549.2 | ||
OTX1 | ENST00000366671.7 | c.137C>A | p.Thr46Lys | missense_variant | Exon 4 of 5 | 3 | ENSP00000355631.3 | |||
OTX1 | ENST00000405984.8 | n.252C>A | non_coding_transcript_exon_variant | Exon 4 of 5 | 2 | ENSP00000385782.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459674Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726176
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.137C>A (p.T46K) alteration is located in exon 4 (coding exon 2) of the OTX1 gene. This alteration results from a C to A substitution at nucleotide position 137, causing the threonine (T) at amino acid position 46 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at