19-33205524-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002333.4(LRP3):c.754C>A(p.Leu252Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,565,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002333.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP3 | ENST00000253193.9 | c.754C>A | p.Leu252Met | missense_variant | 5/7 | 1 | NM_002333.4 | ENSP00000253193.6 | ||
LRP3 | ENST00000590275.1 | n.1068C>A | non_coding_transcript_exon_variant | 3/3 | 2 | |||||
LRP3 | ENST00000590278.1 | n.1655C>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000113 AC: 20AN: 176680Hom.: 0 AF XY: 0.000154 AC XY: 15AN XY: 97502
GnomAD4 exome AF: 0.0000453 AC: 64AN: 1413778Hom.: 0 Cov.: 31 AF XY: 0.0000787 AC XY: 55AN XY: 699170
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 34 AF XY: 0.0000941 AC XY: 7AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2023 | The c.754C>A (p.L252M) alteration is located in exon 5 (coding exon 5) of the LRP3 gene. This alteration results from a C to A substitution at nucleotide position 754, causing the leucine (L) at amino acid position 252 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at