rs1399824473
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_001370259.2(MEN1):c.49G>A(p.Asp17Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,188 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. D17G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001370259.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.49G>A | p.Asp17Asn | missense_variant | 2/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.49G>A | p.Asp17Asn | missense_variant | 2/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151512Hom.: 0 Cov.: 30
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455676Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 723814
GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151512Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 73986
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 17 of the MEN1 protein (p.Asp17Asn). This variant is present in population databases (no rsID available, gnomAD 0.06%). 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: 527272). 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) performed at Invitae indicates that this missense variant is expected to disrupt 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 | Aug 11, 2021 | The p.D17N variant (also known as c.49G>A), located in coding exon 1 of the MEN1 gene, results from a G to A substitution at nucleotide position 49. The aspartic acid at codon 17 is replaced by asparagine, 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