rs786200964
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePM2BP6
The NM_001134831.2(AHI1):c.2961+7_2961+21delinsGACTTTTTTAAAGTTTTAAA variant causes a splice donor, splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
AHI1
NM_001134831.2 splice_donor, splice_donor_5th_base, intron
NM_001134831.2 splice_donor, splice_donor_5th_base, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.63
Genes affected
AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.054580897 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.5, offset of 0 (no position change), new splice context is: acaGTaagt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 6-135411327-AACTGCATAAAATAA-TTTAAAACTTTAAAAAAGTC is Benign according to our data. Variant chr6-135411327-AACTGCATAAAATAA-TTTAAAACTTTAAAAAAGTC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 166663.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.2961+7_2961+21delinsGACTTTTTTAAAGTTTTAAA | splice_donor_variant, splice_donor_5th_base_variant, intron_variant | ENST00000265602.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.2961+7_2961+21delinsGACTTTTTTAAAGTTTTAAA | splice_donor_variant, splice_donor_5th_base_variant, intron_variant | 1 | NM_001134831.2 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 19, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2019 | This variant is associated with the following publications: (PMID: 22334370) - |
Familial aplasia of the vermis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at