11-2885126-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001122630.2(CDKN1C):c.331G>A(p.Ala111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 1,471,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. A111S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122630.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152020Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000661 AC: 5AN: 75610Hom.: 0 AF XY: 0.0000238 AC XY: 1AN XY: 41956
GnomAD4 exome AF: 0.0000182 AC: 24AN: 1319420Hom.: 0 Cov.: 31 AF XY: 0.0000170 AC XY: 11AN XY: 648370
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Beckwith-Wiedemann syndrome;C1846009:IMAGe syndrome Uncertain:1
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Beckwith-Wiedemann syndrome Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 122 of the CDKN1C protein (p.Ala122Thr). This variant is present in population databases (rs551863674, gnomAD 0.06%). This missense change has been observed in individual(s) with choroid plexus papilloma (PMID: 37204857). ClinVar contains an entry for this variant (Variation ID: 567058). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. -
Inborn genetic diseases Uncertain:1
The c.364G>A (p.A122T) alteration is located in exon 1 (coding exon 1) of the CDKN1C gene. This alteration results from a G to A substitution at nucleotide position 364, causing the alanine (A) at amino acid position 122 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at