rs757222534
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_019892.6(INPP5E):c.1468G>T(p.Asp490Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,611,150 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D490V) has been classified as Uncertain significance.
Frequency
Consequence
NM_019892.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.1468G>T | p.Asp490Tyr | missense_variant | 7/10 | ENST00000371712.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1468G>T | p.Asp490Tyr | missense_variant | 7/10 | 1 | NM_019892.6 | P1 | |
INPP5E | ENST00000676019.1 | c.1366G>T | p.Asp456Tyr | missense_variant | 7/10 |
Frequencies
GnomAD3 genomes ? AF: 0.0000133 AC: 2AN: 150882Hom.: 0 Cov.: 30
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460268Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3AN XY: 726456
GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 150882Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1AN XY: 73594
ClinVar
Submissions by phenotype
Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 19, 2024 | Variant summary: INPP5E c.1468G>T (p.Asp490Tyr) results in a non-conservative amino acid change located in the Inositol polyphosphate-related phosphatase domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246596 control chromosomes. c.1468G>T has been reported in the literature in individuals affected with Joubert Syndrome And Related Disorders. These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. ClinVar contains an entry for this variant (Variation ID: 217665). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at