11-68363818-C-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_002335.4(LRP5):c.758C>T(p.Thr253Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T253K) has been classified as Uncertain significance.
Frequency
Consequence
NM_002335.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP5 | NM_002335.4 | c.758C>T | p.Thr253Ile | missense_variant | 4/23 | ENST00000294304.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP5 | ENST00000294304.12 | c.758C>T | p.Thr253Ile | missense_variant | 4/23 | 1 | NM_002335.4 | P1 | |
LRP5 | ENST00000529993.5 | c.758C>T | p.Thr253Ile | missense_variant, NMD_transcript_variant | 4/23 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 28
ClinVar
Submissions by phenotype
Autosomal dominant osteopetrosis 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2003 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at