9-136433044-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_019892.6(INPP5E):c.1191C>A(p.Ile397=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,524 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 (★). Synonymous variant affecting the same amino acid position (i.e. I397I) has been classified as Likely benign.
Frequency
Consequence
NM_019892.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5E | NM_019892.6 | c.1191C>A | p.Ile397= | synonymous_variant | 5/10 | ENST00000371712.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5E | ENST00000371712.4 | c.1191C>A | p.Ile397= | synonymous_variant | 5/10 | 1 | NM_019892.6 | P1 | |
INPP5E | ENST00000676019.1 | c.1089C>A | p.Ile363= | synonymous_variant | 5/10 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250380Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135722
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461348Hom.: 0 Cov.: 54 AF XY: 0.00000413 AC XY: 3AN XY: 726970
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
Familial aplasia of the vermis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1417138). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change affects codon 397 of the INPP5E mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the INPP5E protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at