1-241497839-CCAG-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate
The NM_000143.4(FH):c.1519_1521delCTG(p.Leu507del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L507L) has been classified as Likely benign.
Frequency
Consequence
NM_000143.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FH | NM_000143.4 | c.1519_1521delCTG | p.Leu507del | conservative_inframe_deletion | Exon 10 of 10 | ENST00000366560.4 | NP_000134.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
The c.1519_1521delCTG variant (also known as p.L507del) is located in coding exon 10 of the FH gene. This variant results from an in-frame CTG deletion at nucleotide positions 1519 to 1521. A close-match alteration, FH c.1520T>C (P.L507P) is considered likely pathogenic and highlights the clinical importance of this residue (Ambry internal data; Alam NA et al. J Mol Diagn, 2005 Oct;7:437-43). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with FH-related disease (Ambry internal data). Based on internal structural analysis, this variant decreases structural stability and protein-protein binding (Ajalla Aleixo MA et al. FEBS J, 2019 05;286:1925-1940). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.