11-64809935-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_001370259.2(MEN1):c.175C>G(p.Pro59Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001370259.2 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.175C>G | p.Pro59Ala | missense_variant | 2/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.175C>G | p.Pro59Ala | missense_variant | 2/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 30
GnomAD4 exome Cov.: 35
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 527274). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 59 of the MEN1 protein (p.Pro59Ala). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 31, 2023 | The p.P59A variant (also known as c.175C>G), located in coding exon 1 of the MEN1 gene, results from a C to G substitution at nucleotide position 175. The proline at codon 59 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at