rs1477382841
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001122630.2(CDKN1C):c.98G>T(p.Arg33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,435,874 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. R33C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122630.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1C | NM_001122630.2 | c.98G>T | p.Arg33Leu | missense_variant | 2/4 | ENST00000440480.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1C | ENST00000440480.8 | c.98G>T | p.Arg33Leu | missense_variant | 2/4 | 1 | NM_001122630.2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000496 AC: 1AN: 201738Hom.: 0 AF XY: 0.00000907 AC XY: 1AN XY: 110290
GnomAD4 exome AF: 0.00000279 AC: 4AN: 1435874Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1AN XY: 712564
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Beckwith-Wiedemann syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 24, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 25, 2023 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 44 of the CDKN1C protein (p.Arg44Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDKN1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 453990). 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 not expected to disrupt CDKN1C protein function with a negative predictive value of 80%. 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. - |
Beckwith-Wiedemann syndrome;C1846009:IMAGe syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 12, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at