rs756736858
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001099403.2(PRDM8):c.868G>A(p.Gly290Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000818 in 1,589,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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 Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.868G>A | p.Gly290Ser | missense_variant | 4/4 | ENST00000415738.3 | |
PRDM8 | NM_020226.4 | c.868G>A | p.Gly290Ser | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.868G>A | p.Gly290Ser | missense_variant | 4/4 | 1 | NM_001099403.2 | P1 | |
PRDM8 | ENST00000339711.8 | c.868G>A | p.Gly290Ser | missense_variant | 10/10 | 1 | P1 | ||
PRDM8 | ENST00000515013.5 | c.868G>A | p.Gly290Ser | missense_variant | 10/10 | 1 | |||
PRDM8 | ENST00000504452.5 | c.868G>A | p.Gly290Ser | missense_variant | 8/8 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151774Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000373 AC: 8AN: 214228Hom.: 0 AF XY: 0.0000253 AC XY: 3AN XY: 118714
GnomAD4 exome AF: 0.00000834 AC: 12AN: 1438204Hom.: 0 Cov.: 36 AF XY: 0.00000419 AC XY: 3AN XY: 715338
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151774Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74104
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2023 | The c.868G>A (p.G290S) alteration is located in exon 10 (coding exon 3) of the PRDM8 gene. This alteration results from a G to A substitution at nucleotide position 868, causing the glycine (G) at amino acid position 290 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Early-onset Lafora body disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces glycine with serine at codon 290 of the PRDM8 protein (p.Gly290Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs756736858, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with PRDM8-related conditions. ClinVar contains an entry for this variant (Variation ID: 542338). 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 serine 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