rs749001511
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001370259.2(MEN1):c.177C>T(p.Pro59Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001370259.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.177C>T | p.Pro59Pro | synonymous_variant | Exon 2 of 10 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432168Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 710172
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1
This sequence change affects codon 59 of the MEN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MEN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with symptoms consistent with multiple endocrine neoplasia type 1 (MEN1) (Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. -
Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at