chr4-80202449-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001099403.2(PRDM8):c.987G>A(p.Leu329Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,394,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L329L) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000065 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PRDM8
NM_001099403.2 synonymous
NM_001099403.2 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.10
Publications
4 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 -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP7
Synonymous conserved (PhyloP=1.1 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PRDM8 | NM_001099403.2 | c.987G>A | p.Leu329Leu | synonymous_variant | Exon 4 of 4 | ENST00000415738.3 | NP_001092873.1 | |
| PRDM8 | NM_020226.4 | c.987G>A | p.Leu329Leu | synonymous_variant | Exon 10 of 10 | NP_064611.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PRDM8 | ENST00000415738.3 | c.987G>A | p.Leu329Leu | synonymous_variant | Exon 4 of 4 | 1 | NM_001099403.2 | ENSP00000406998.2 | ||
| PRDM8 | ENST00000339711.8 | c.987G>A | p.Leu329Leu | synonymous_variant | Exon 10 of 10 | 1 | ENSP00000339764.4 | |||
| PRDM8 | ENST00000515013.5 | c.987G>A | p.Leu329Leu | synonymous_variant | Exon 10 of 10 | 1 | ENSP00000425149.1 | |||
| PRDM8 | ENST00000504452.5 | c.987G>A | p.Leu329Leu | synonymous_variant | Exon 8 of 8 | 5 | ENSP00000423985.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151932Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151932
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000645 AC: 9AN: 1394410Hom.: 0 Cov.: 37 AF XY: 0.00000581 AC XY: 4AN XY: 688014 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1394410
Hom.:
Cov.:
37
AF XY:
AC XY:
4
AN XY:
688014
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31420
American (AMR)
AF:
AC:
0
AN:
35328
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25090
East Asian (EAS)
AF:
AC:
0
AN:
35762
South Asian (SAS)
AF:
AC:
0
AN:
79246
European-Finnish (FIN)
AF:
AC:
0
AN:
45540
Middle Eastern (MID)
AF:
AC:
0
AN:
5466
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1078726
Other (OTH)
AF:
AC:
0
AN:
57832
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
30-35
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>80
Age
GnomAD4 genome 0.00000658 AC: 1AN: 151932Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74222 show subpopulations
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
151932
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74222
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41354
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5134
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67962
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational 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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