rs121909489
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001174147.2(LMX1B):c.244C>T(p.Gln82*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001174147.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LMX1B | NM_001174147.2 | c.244C>T | p.Gln82* | stop_gained | Exon 2 of 8 | ENST00000373474.9 | NP_001167618.1 | |
LMX1B | NM_001174146.2 | c.244C>T | p.Gln82* | stop_gained | Exon 2 of 8 | NP_001167617.1 | ||
LMX1B | NM_002316.4 | c.244C>T | p.Gln82* | stop_gained | Exon 2 of 8 | NP_002307.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMX1B | ENST00000373474.9 | c.244C>T | p.Gln82* | stop_gained | Exon 2 of 8 | 1 | NM_001174147.2 | ENSP00000362573.3 | ||
LMX1B | ENST00000355497.10 | c.244C>T | p.Gln82* | stop_gained | Exon 2 of 8 | 1 | ENSP00000347684.5 | |||
LMX1B | ENST00000526117.6 | c.244C>T | p.Gln82* | stop_gained | Exon 2 of 8 | 1 | ENSP00000436930.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1459496Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726122
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:2
The Q82X variant in the LMX1B gene has been reported previously, using alternate nomenclature as Gln59Ter, in multiple affected individuals from a large family with nail patella syndrome (Vollrath et al., 1998). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q82X variant is not observed in large population cohorts (Lek et al., 2016). We interpret Q82X as a pathogenic variant. -
This sequence change creates a premature translational stop signal (p.Gln82*) in the LMX1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMX1B are known to be pathogenic (PMID: 9590287, 15498463). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with nail-patella syndrome (PMID: 9618165). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Gln59Ter. ClinVar contains an entry for this variant (Variation ID: 7005). For these reasons, this variant has been classified as Pathogenic. -
Nail-patella syndrome;C0403548:Nail-patella-like renal disease Pathogenic:1
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Nail-patella syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at