4-80200198-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001099403.2(PRDM8):āc.118A>Gā(p.Ile40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,964 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 (ā ).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.118A>G | p.Ile40Val | missense_variant | 2/4 | ENST00000415738.3 | NP_001092873.1 | |
PRDM8 | NM_020226.4 | c.118A>G | p.Ile40Val | missense_variant | 8/10 | NP_064611.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.118A>G | p.Ile40Val | missense_variant | 2/4 | 1 | NM_001099403.2 | ENSP00000406998 | P1 | |
PRDM8 | ENST00000339711.8 | c.118A>G | p.Ile40Val | missense_variant | 8/10 | 1 | ENSP00000339764 | P1 | ||
PRDM8 | ENST00000515013.5 | c.118A>G | p.Ile40Val | missense_variant | 8/10 | 1 | ENSP00000425149 | |||
PRDM8 | ENST00000504452.5 | c.118A>G | p.Ile40Val | missense_variant | 6/8 | 5 | ENSP00000423985 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249584Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135408
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461804Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727216
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Early-onset Lafora body disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 16, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 40 of the PRDM8 protein (p.Ile40Val). This variant is present in population databases (rs772463473, gnomAD 0.007%). 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: 1475554). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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