chr21-46228665-AGTCGCGCTCTCCTCAGCACCTAGGACCACCCCGCATTCGTCAGGAGCCCGGGGCGAGGGGACTCACGTGCCCTCCGTCATTGCTGCTGCAGTGCTCTACGCCGCCCACTGCCAGCTGCCAGATGTCCGCACCCGGGACCTGCCGCCCAGCCCCGCCCCTCCCGCCCCTCCCGCCCCTCCCGCCCCTCCCGCGCGCACTACGCAGGCGCAGGCCTCGGCAGGCGCTCAGGCTTAGGTGGGCCGACGCCCACGCAACCAATCAGAGCGCCGCGAGCGTGACCCCGGGGTGTGCCAGGCGACCACAGTGGTGGAGCGCTTGGTGCCCCATGCGGCGTGGGGC-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_002340.6(LSS):c.-259_14+66del variant causes a exon loss, splice region 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
LSS
NM_002340.6 exon_loss, splice_region
NM_002340.6 exon_loss, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.451
Genes affected
LSS (HGNC:6708): (lanosterol synthase) The protein encoded by this gene catalyzes the conversion of (S)-2,3 oxidosqualene to lanosterol. The encoded protein is a member of the terpene cyclase/mutase family and catalyzes the first step in the biosynthesis of cholesterol, steroid hormones, and vitamin D. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 21-46228665-AGTCGCGCTCTCCTCAGCACCTAGGACCACCCCGCATTCGTCAGGAGCCCGGGGCGAGGGGACTCACGTGCCCTCCGTCATTGCTGCTGCAGTGCTCTACGCCGCCCACTGCCAGCTGCCAGATGTCCGCACCCGGGACCTGCCGCCCAGCCCCGCCCCTCCCGCCCCTCCCGCCCCTCCCGCCCCTCCCGCGCGCACTACGCAGGCGCAGGCCTCGGCAGGCGCTCAGGCTTAGGTGGGCCGACGCCCACGCAACCAATCAGAGCGCCGCGAGCGTGACCCCGGGGTGTGCCAGGCGACCACAGTGGTGGAGCGCTTGGTGCCCCATGCGGCGTGGGGC-A is Pathogenic according to our data. Variant chr21-46228665-AGTCGCGCTCTCCTCAGCACCTAGGACCACCCCGCATTCGTCAGGAGCCCGGGGCGAGGGGACTCACGTGCCCTCCGTCATTGCTGCTGCAGTGCTCTACGCCGCCCACTGCCAGCTGCCAGATGTCCGCACCCGGGACCTGCCGCCCAGCCCCGCCCCTCCCGCCCCTCCCGCCCCTCCCGCCCCTCCCGCGCGCACTACGCAGGCGCAGGCCTCGGCAGGCGCTCAGGCTTAGGTGGGCCGACGCCCACGCAACCAATCAGAGCGCCGCGAGCGTGACCCCGGGGTGTGCCAGGCGACCACAGTGGTGGAGCGCTTGGTGCCCCATGCGGCGTGGGGC-A is described in ClinVar as [Pathogenic]. Clinvar id is 1707554.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LSS | NM_002340.6 | c.-259_14+66del | exon_loss_variant, splice_region_variant | 1/22 | ENST00000397728.8 | NP_002331.3 | ||
| LSS | NM_002340.6 | c.-259_14+66del | splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant | 1/22 | ENST00000397728.8 | NP_002331.3 | ||
| LSS | NM_002340.6 | c.-259_14+66del | upstream_gene_variant | ENST00000397728.8 | NP_002331.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LSS | ENST00000397728.8 | c.-259_14+66del | exon_loss_variant, splice_region_variant | 1/22 | 1 | NM_002340.6 | ENSP00000380837.2 | |||
| LSS | ENST00000397728.8 | c.-259_14+66del | splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, splice_region_variant, intron_variant | 1/22 | 1 | NM_002340.6 | ENSP00000380837.2 | |||
| LSS | ENST00000397728.8 | c.-259_14+66del | upstream_gene_variant | 1 | NM_002340.6 | ENSP00000380837.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Alopecia-intellectual disability syndrome 4 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.