rs376696104
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006031.6(PCNT):āc.8951C>Gā(p.Ser2984Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,611,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_006031.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.8951C>G | p.Ser2984Cys | missense_variant | 39/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.8360C>G | p.Ser2787Cys | missense_variant | 39/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.8951C>G | p.Ser2984Cys | missense_variant | 39/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000542 AC: 13AN: 239902Hom.: 0 AF XY: 0.0000304 AC XY: 4AN XY: 131372
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1458764Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 725874
GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74486
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 13, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 18, 2022 | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2984 of the PCNT protein (p.Ser2984Cys). This variant is present in population databases (rs376696104, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 436274). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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