rs761079352
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000077.5(CDKN2A):c.128G>C(p.Ser43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S43G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000077.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.128G>C | p.Ser43Thr | missense_variant | 1/3 | ENST00000304494.10 | |
CDKN2A | NM_058195.4 | c.194-3492G>C | intron_variant | ENST00000579755.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.128G>C | p.Ser43Thr | missense_variant | 1/3 | 1 | NM_000077.5 | P2 | |
CDKN2A | ENST00000579755.2 | c.194-3492G>C | intron_variant | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 43 of the CDKN2A (p16INK4a) protein (p.Ser43Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. ClinVar contains an entry for this variant (Variation ID: 569634). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at