11-64809985-CCCAGCA-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001370259.2(MEN1):c.119_124delTGCTGG(p.Val40_Leu41del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001370259.2 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.119_124delTGCTGG | p.Val40_Leu41del | disruptive_inframe_deletion | Exon 2 of 10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: MEN1 c.119_124delTGCTGG (p.Val40_Leu41del) results in an in-frame deletion that is predicted to remove two amino acids (Val, Leu) from the encoded protein. The variant was absent in 217338 control chromosomes (in gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.119_124delTGCTGG in individuals affected with Multiple Endocrine Neoplasia Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Multiple endocrine neoplasia, type 1 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has been observed in an individual affected with multiple endocrine neoplasia type 1 (PMID: 26767918). ClinVar contains an entry for this variant (Variation ID: 36522). This variant is not present in population databases (ExAC no frequency). This variant, c.119_124delTGCTGG, results in the deletion of 2 amino acid(s) of the MEN1 protein (p.Val40_Leu41del), but otherwise preserves the integrity of the reading frame. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at