rs762557383
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001099403.2(PRDM8):c.164T>A(p.Ile55Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000713 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I55V) has been classified 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.164T>A | p.Ile55Lys | missense_variant | 2/4 | ENST00000415738.3 | |
PRDM8 | NM_020226.4 | c.164T>A | p.Ile55Lys | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.164T>A | p.Ile55Lys | missense_variant | 2/4 | 1 | NM_001099403.2 | P1 | |
PRDM8 | ENST00000339711.8 | c.164T>A | p.Ile55Lys | missense_variant | 8/10 | 1 | P1 | ||
PRDM8 | ENST00000515013.5 | c.164T>A | p.Ile55Lys | missense_variant | 8/10 | 1 | |||
PRDM8 | ENST00000504452.5 | c.164T>A | p.Ile55Lys | missense_variant | 6/8 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249578Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135406
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.0000756 AC XY: 55AN XY: 727216
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Early-onset Lafora body disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 55 of the PRDM8 protein (p.Ile55Lys). This variant is present in population databases (rs762557383, gnomAD 0.004%). 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: 565874). 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