rs774459714
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001099403.2(PRDM8):āc.1674T>Cā(p.Gly558=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 1,558,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000092 ( 0 hom. )
Consequence
PRDM8
NM_001099403.2 synonymous
NM_001099403.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0240
Genes affected
PRDM8 (HGNC:13993): (PR/SET domain 8) This gene encodes a protein that belongs to a conserved family of histone methyltransferases that predominantly act as negative regulators of transcription. The encoded protein contains an N-terminal Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain and a double zinc-finger domain. Knockout of this gene in mouse results in mistargeting by neurons of the dorsal telencephalon, abnormal itch-like behavior, and impaired differentiation of rod bipolar cells. In humans, the protein has been shown to interact with the phosphatase laforin and the ubiquitin ligase malin, which regulate glycogen construction in the cytoplasm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 4-80203136-T-C is Benign according to our data. Variant chr4-80203136-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 542344.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.1674T>C | p.Gly558= | synonymous_variant | 4/4 | ENST00000415738.3 | |
PRDM8 | NM_020226.4 | c.1674T>C | p.Gly558= | synonymous_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.1674T>C | p.Gly558= | synonymous_variant | 4/4 | 1 | NM_001099403.2 | P1 | |
PRDM8 | ENST00000339711.8 | c.1674T>C | p.Gly558= | synonymous_variant | 10/10 | 1 | P1 | ||
PRDM8 | ENST00000504452.5 | c.1674T>C | p.Gly558= | synonymous_variant | 8/8 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000664 AC: 1AN: 150588Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000579 AC: 9AN: 155416Hom.: 0 AF XY: 0.0000347 AC XY: 3AN XY: 86566
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GnomAD4 exome AF: 0.00000923 AC: 13AN: 1407728Hom.: 0 Cov.: 36 AF XY: 0.00000573 AC XY: 4AN XY: 697520
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early-onset Lafora body disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at