rs766996989
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004064.5(CDKN1B):āc.386A>Gā(p.His129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. H129Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_004064.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1B | NM_004064.5 | c.386A>G | p.His129Arg | missense_variant | 1/3 | ENST00000228872.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1B | ENST00000228872.9 | c.386A>G | p.His129Arg | missense_variant | 1/3 | 1 | NM_004064.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151806Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1454450Hom.: 0 Cov.: 38 AF XY: 0.00000276 AC XY: 2AN XY: 723670
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151922Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 4 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 129 of the CDKN1B protein (p.His129Arg). This variant is present in population databases (rs766996989, gnomAD no frequency). 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: 485498). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 25, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2022 | The p.H129R variant (also known as c.386A>G), located in coding exon 1 of the CDKN1B gene, results from an A to G substitution at nucleotide position 386. The histidine at codon 129 is replaced by arginine, an amino acid with highly similar 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