chr9-136429687-GC-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_019892.6(INPP5E):c.1922delG(p.Cys641SerfsTer8) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_019892.6 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.1922delG | p.Cys641SerfsTer8 | frameshift_variant | Exon 10 of 10 | ENST00000371712.4 | NP_063945.2 | |
INPP5E | NM_001318502.2 | c.1919delG | p.Cys640SerfsTer8 | frameshift_variant | Exon 10 of 10 | NP_001305431.1 | ||
INPP5E | XM_017014926.2 | c.*66delG | 3_prime_UTR_variant | Exon 10 of 10 | XP_016870415.1 | |||
INPP5E | XM_047423603.1 | c.*66delG | 3_prime_UTR_variant | Exon 10 of 10 | XP_047279559.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1922delG | p.Cys641SerfsTer8 | frameshift_variant | Exon 10 of 10 | 1 | NM_019892.6 | ENSP00000360777.3 | ||
INPP5E | ENST00000676019.1 | c.1820delG | p.Cys607SerfsTer8 | frameshift_variant | Exon 10 of 10 | ENSP00000501984.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251450Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135908
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461728Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727158
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial aplasia of the vermis Pathogenic:1
This sequence change results in a frameshift in the INPP5E gene (p.Cys641Serfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the INPP5E protein and extend the protein by 3 additional amino acid residues. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. ClinVar contains an entry for this variant (Variation ID: 581255). This variant disrupts a region of the INPP5E protein in which other variant(s) (p.Cys641Arg) have been determined to be pathogenic (PMID: 23386033). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at