rs1057520178
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001174147.2(LMX1B):c.285_289del(p.Tyr95Ter) variant causes a stop gained, frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
LMX1B
NM_001174147.2 stop_gained, frameshift
NM_001174147.2 stop_gained, frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.42
Genes affected
LMX1B (HGNC:6654): (LIM homeobox transcription factor 1 beta) This gene encodes a member of LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-126615527-ACTTCC-A is Pathogenic according to our data. Variant chr9-126615527-ACTTCC-A is described in ClinVar as [Pathogenic]. Clinvar id is 377264.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMX1B | NM_001174147.2 | c.285_289del | p.Tyr95Ter | stop_gained, frameshift_variant | 2/8 | ENST00000373474.9 | |
LMX1B | NM_001174146.2 | c.285_289del | p.Tyr95Ter | stop_gained, frameshift_variant | 2/8 | ||
LMX1B | NM_002316.4 | c.285_289del | p.Tyr95Ter | stop_gained, frameshift_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMX1B | ENST00000373474.9 | c.285_289del | p.Tyr95Ter | stop_gained, frameshift_variant | 2/8 | 1 | NM_001174147.2 | P4 | |
LMX1B | ENST00000355497.10 | c.285_289del | p.Tyr95Ter | stop_gained, frameshift_variant | 2/8 | 1 | |||
LMX1B | ENST00000526117.6 | c.285_289del | p.Tyr95Ter | stop_gained, frameshift_variant | 2/8 | 1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 02, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at