chr9-130664712-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021619.3(PRDM12):c.59C>A(p.Pro20Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P20R) has been classified as Uncertain significance.
Frequency
Consequence
NM_021619.3 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 |
---|---|---|---|---|---|---|---|
PRDM12 | NM_021619.3 | c.59C>A | p.Pro20Gln | missense_variant | 1/5 | ENST00000253008.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM12 | ENST00000253008.3 | c.59C>A | p.Pro20Gln | missense_variant | 1/5 | 1 | NM_021619.3 | P1 | |
PRDM12 | ENST00000676323.1 | c.59C>A | p.Pro20Gln | missense_variant | 1/6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000422 AC: 1AN: 237100Hom.: 0 AF XY: 0.00000766 AC XY: 1AN XY: 130494
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457558Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 725090
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Congenital insensitivity to pain-hypohidrosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 01, 2021 | This variant has not been reported in the literature in individuals affected with PRDM12-related conditions. 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. 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with glutamine at codon 20 of the PRDM12 protein (p.Pro20Gln). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at