chr3-124347234-AGAGGCATGATGACTTTGAAGAGGTGGCTCAGGTGAGAAGCTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTCTAGATGAGG-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PVS1_ModeratePP3BP6_Moderate
The NM_001388419.1(KALRN):c.1770+43_1770+139del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KALRN
NM_001388419.1 splice_donor, splice_donor_5th_base, coding_sequence, intron
NM_001388419.1 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.013614552 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP6
Variant 3-124347234-AGAGGCATGATGACTTTGAAGAGGTGGCTCAGGTGAGAAGCTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTCTAGATGAGG-A is Benign according to our data. Variant chr3-124347234-AGAGGCATGATGACTTTGAAGAGGTGGCTCAGGTGAGAAGCTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTCTAGATGAGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033496.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KALRN | NM_001388419.1 | c.1770+43_1770+139del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 10/60 | ENST00000682506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KALRN | ENST00000682506.1 | c.1770+43_1770+139del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 10/60 | NM_001388419.1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 5AN: 147912Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000144 AC: 21AN: 1460174Hom.: 0 AF XY: 0.0000165 AC XY: 12AN XY: 726408
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000338 AC: 5AN: 148028Hom.: 0 Cov.: 32 AF XY: 0.0000554 AC XY: 4AN XY: 72148
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KALRN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 29, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.