rs431825171
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_020347.4(LZTFL1):c.402_406del(p.Pro136ThrfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
LZTFL1
NM_020347.4 frameshift
NM_020347.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.31
Genes affected
LZTFL1 (HGNC:6741): (leucine zipper transcription factor like 1) This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 3-45833099-GGCTTT-G is Pathogenic according to our data. Variant chr3-45833099-GGCTTT-G is described in ClinVar as [Pathogenic]. Clinvar id is 39770.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-45833099-GGCTTT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTFL1 | NM_020347.4 | c.402_406del | p.Pro136ThrfsTer5 | frameshift_variant | 5/10 | ENST00000296135.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTFL1 | ENST00000296135.11 | c.402_406del | p.Pro136ThrfsTer5 | frameshift_variant | 5/10 | 1 | NM_020347.4 | P1 | |
ENST00000699185.1 | n.3796+5701_3796+5705del | intron_variant, non_coding_transcript_variant |
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: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome 17 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at