rs758969495
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001099403.2(PRDM8):c.1955A>G(p.Tyr652Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y652Y) has been classified as Likely benign.
Frequency
Consequence
NM_001099403.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.1955A>G | p.Tyr652Cys | missense_variant | 4/4 | ENST00000415738.3 | |
PRDM8 | NM_020226.4 | c.1955A>G | p.Tyr652Cys | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.1955A>G | p.Tyr652Cys | missense_variant | 4/4 | 1 | NM_001099403.2 | P1 | |
PRDM8 | ENST00000339711.8 | c.1955A>G | p.Tyr652Cys | missense_variant | 10/10 | 1 | P1 | ||
PRDM8 | ENST00000504452.5 | c.1955A>G | p.Tyr652Cys | missense_variant | 8/8 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248310Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134832
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461580Hom.: 0 Cov.: 36 AF XY: 0.00000688 AC XY: 5AN XY: 727032
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Early-onset Lafora body disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2021 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PRDM8-related disease. This variant is present in population databases (rs758969495, ExAC 0.003%). This sequence change replaces tyrosine with cysteine at codon 652 of the PRDM8 protein (p.Tyr652Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at