NM_001099403.2:c.451+13G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001099403.2(PRDM8):c.451+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,457,750 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
PRDM8
NM_001099403.2 intron
NM_001099403.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.680
Publications
1 publications found
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]
PRDM8 Gene-Disease associations (from GenCC):
- early-onset Lafora body diseaseInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 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 4-80201534-G-A is Benign according to our data. Variant chr4-80201534-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3719310.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM8 | NM_001099403.2 | c.451+13G>A | intron_variant | Intron 3 of 3 | ENST00000415738.3 | NP_001092873.1 | ||
PRDM8 | NM_020226.4 | c.451+13G>A | intron_variant | Intron 9 of 9 | NP_064611.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM8 | ENST00000415738.3 | c.451+13G>A | intron_variant | Intron 3 of 3 | 1 | NM_001099403.2 | ENSP00000406998.2 | |||
PRDM8 | ENST00000339711.8 | c.451+13G>A | intron_variant | Intron 9 of 9 | 1 | ENSP00000339764.4 | ||||
PRDM8 | ENST00000515013.5 | c.451+13G>A | intron_variant | Intron 9 of 9 | 1 | ENSP00000425149.1 | ||||
PRDM8 | ENST00000504452.5 | c.451+13G>A | intron_variant | Intron 7 of 7 | 5 | ENSP00000423985.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000403 AC: 1AN: 248034 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
248034
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000686 AC: 10AN: 1457750Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5AN XY: 725354 show subpopulations
GnomAD4 exome
AF:
AC:
10
AN:
1457750
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
725354
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33378
American (AMR)
AF:
AC:
0
AN:
44668
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
26100
East Asian (EAS)
AF:
AC:
0
AN:
39670
South Asian (SAS)
AF:
AC:
0
AN:
86158
European-Finnish (FIN)
AF:
AC:
0
AN:
53386
Middle Eastern (MID)
AF:
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1108410
Other (OTH)
AF:
AC:
0
AN:
60242
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
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5
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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
Sep 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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