rs775267651
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001370259.2(MEN1):āc.1166G>Cā(p.Arg389Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R389Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001370259.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.1166G>C | p.Arg389Pro | missense_variant | 8/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.1166G>C | p.Arg389Pro | missense_variant | 8/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727174
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 21, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 389 of the MEN1 protein (p.Arg389Pro). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 646507). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MEN1 protein function. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The p.R389P variant (also known as c.1166G>C), located in coding exon 7 of the MEN1 gene, results from a G to C substitution at nucleotide position 1166. The arginine at codon 389 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is well 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