rs1014065137
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001099403.2(PRDM8):c.1450G>A(p.Gly484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000966 in 1,345,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001099403.2 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 |
---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.1450G>A | p.Gly484Ser | missense_variant | 4/4 | ENST00000415738.3 | |
PRDM8 | NM_020226.4 | c.1450G>A | p.Gly484Ser | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.1450G>A | p.Gly484Ser | missense_variant | 4/4 | 1 | NM_001099403.2 | P1 | |
PRDM8 | ENST00000339711.8 | c.1450G>A | p.Gly484Ser | missense_variant | 10/10 | 1 | P1 | ||
PRDM8 | ENST00000504452.5 | c.1450G>A | p.Gly484Ser | missense_variant | 8/8 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000397 AC: 6AN: 151274Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000586 AC: 7AN: 1193822Hom.: 0 Cov.: 36 AF XY: 0.00000344 AC XY: 2AN XY: 580796
GnomAD4 genome ? AF: 0.0000396 AC: 6AN: 151382Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73992
ClinVar
Submissions by phenotype
Early-onset Lafora body disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2020 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PRDM8-related disease. 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 sequence change replaces glycine with serine at codon 484 of the PRDM8 protein (p.Gly484Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at