rs771866500
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_019892.6(INPP5E):āc.1565G>Cā(p.Gly522Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,550 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 Pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G522R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_019892.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.1565G>C | p.Gly522Ala | missense_variant | 8/10 | ENST00000371712.4 | |
INPP5E | NM_001318502.2 | c.1562G>C | p.Gly521Ala | missense_variant | 8/10 | ||
INPP5E | XM_017014926.2 | c.1565G>C | p.Gly522Ala | missense_variant | 8/10 | ||
INPP5E | XM_047423603.1 | c.1562G>C | p.Gly521Ala | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1565G>C | p.Gly522Ala | missense_variant | 8/10 | 1 | NM_019892.6 | P1 | |
INPP5E | ENST00000676019.1 | c.1463G>C | p.Gly488Ala | missense_variant | 8/10 | ||||
INPP5E | ENST00000674693.1 | n.82G>C | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151672Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 249968Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135510
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460878Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726788
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151672Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74066
ClinVar
Submissions by phenotype
Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt INPP5E protein function. ClinVar contains an entry for this variant (Variation ID: 530891). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 29052317). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs771866500, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 522 of the INPP5E protein (p.Gly522Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at