4-80200244-T-A
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 (★).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.164T>A | p.Ile55Lys | missense_variant | Exon 2 of 4 | ENST00000415738.3 | NP_001092873.1 | |
PRDM8 | NM_020226.4 | c.164T>A | p.Ile55Lys | missense_variant | Exon 8 of 10 | NP_064611.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.164T>A | p.Ile55Lys | missense_variant | Exon 2 of 4 | 1 | NM_001099403.2 | ENSP00000406998.2 | ||
PRDM8 | ENST00000339711.8 | c.164T>A | p.Ile55Lys | missense_variant | Exon 8 of 10 | 1 | ENSP00000339764.4 | |||
PRDM8 | ENST00000515013.5 | c.164T>A | p.Ile55Lys | missense_variant | Exon 8 of 10 | 1 | ENSP00000425149.1 | |||
PRDM8 | ENST00000504452.5 | c.164T>A | p.Ile55Lys | missense_variant | Exon 6 of 8 | 5 | ENSP00000423985.1 |
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
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). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PRDM8 protein function with a negative predictive value of 80%. 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