rs1060500172
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001122630.2(CDKN1C):c.460G>A(p.Val154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 986,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. V154A) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1C | NM_001122630.2 | c.460G>A | p.Val154Ile | missense_variant | 2/4 | ENST00000440480.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1C | ENST00000440480.8 | c.460G>A | p.Val154Ile | missense_variant | 2/4 | 1 | NM_001122630.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000101 AC: 1AN: 986250Hom.: 0 Cov.: 16 AF XY: 0.00000213 AC XY: 1AN XY: 469404
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Beckwith-Wiedemann syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 08, 2020 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a CDKN1C-related disease. This sequence change replaces valine with isoleucine at codon 165 of the CDKN1C protein (p.Val165Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at