rs201806195
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001099403.2(PRDM8):c.721C>T(p.Pro241Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,611,844 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. P241Q) has been classified as Benign.
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.721C>T | p.Pro241Ser | missense_variant | 4/4 | ENST00000415738.3 | |
PRDM8 | NM_020226.4 | c.721C>T | p.Pro241Ser | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.721C>T | p.Pro241Ser | missense_variant | 4/4 | 1 | NM_001099403.2 | P1 | |
PRDM8 | ENST00000339711.8 | c.721C>T | p.Pro241Ser | missense_variant | 10/10 | 1 | P1 | ||
PRDM8 | ENST00000515013.5 | c.721C>T | p.Pro241Ser | missense_variant | 10/10 | 1 | |||
PRDM8 | ENST00000504452.5 | c.721C>T | p.Pro241Ser | missense_variant | 8/8 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000542 AC: 82AN: 151306Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000158 AC: 38AN: 240268Hom.: 0 AF XY: 0.0000986 AC XY: 13AN XY: 131816
GnomAD4 exome AF: 0.0000630 AC: 92AN: 1460418Hom.: 0 Cov.: 38 AF XY: 0.0000551 AC XY: 40AN XY: 726532
GnomAD4 genome ? AF: 0.000542 AC: 82AN: 151426Hom.: 1 Cov.: 31 AF XY: 0.000500 AC XY: 37AN XY: 73982
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2022 | The c.721C>T (p.P241S) alteration is located in exon 10 (coding exon 3) of the PRDM8 gene. This alteration results from a C to T substitution at nucleotide position 721, causing the proline (P) at amino acid position 241 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 | Nov 01, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 241 of the PRDM8 protein (p.Pro241Ser). This variant is present in population databases (rs201806195, gnomAD 0.2%). 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: 542335). 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"). 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