chr11-64804528-C-CCGG
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PM4_SupportingBP6
The NM_001370259.2(MEN1):c.1638_1639insCCG(p.Pro546dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P546P) has been classified as Likely benign.
Frequency
Consequence
NM_001370259.2 inframe_insertion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.1638_1639insCCG | p.Pro546dup | inframe_insertion | 10/10 | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.1638_1639insCCG | p.Pro546dup | inframe_insertion | 10/10 | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251266Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135854
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2023 | This variant, c.1636_1638dup, results in the insertion of 1 amino acid(s) of the MEN1 protein (p.Pro546dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs774350463, 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: 188183). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 22, 2023 | 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