12-12717919-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004064.5(CDKN1B):c.80C>T(p.Ser27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,856 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. S27P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004064.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1B | NM_004064.5 | c.80C>T | p.Ser27Leu | missense_variant | 1/3 | ENST00000228872.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1B | ENST00000228872.9 | c.80C>T | p.Ser27Leu | missense_variant | 1/3 | 1 | NM_004064.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251178Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461856Hom.: 0 Cov.: 52 AF XY: 0.00000275 AC XY: 2AN XY: 727228
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 27 of the CDKN1B protein (p.Ser27Leu). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CDKN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 404282). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 24, 2022 | The p.S27L variant (also known as c.80C>T), located in coding exon 1 of the CDKN1B gene, results from a C to T substitution at nucleotide position 80. The serine at codon 27 is replaced by leucine, an amino acid with dissimilar 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