5-23527372-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_020227.4(PRDM9):āc.2284C>Gā(p.His762Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 11)
Exomes š: 0.0000094 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PRDM9
NM_020227.4 missense
NM_020227.4 missense
Scores
1
1
16
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -20.0
Genes affected
PRDM9 (HGNC:13994): (PR/SET domain 9) The protein encoded by this gene is a zinc finger protein with histone methyltransferase activity that catalyzes histone H3 lysine 4 trimethylation (H3K4me3) during meiotic prophase. This protein contains multiple domains, including a Kruppel-associated box (KRAB) domain, an SSX repression domain (SSXRD), a PRD1-BF1 and RIZ homologous region, a subclass of SET (PR/SET) domain, and a tandem array of C2H2 zinc fingers. The zinc finger array recognizes a short sequence motif, leading to local H3K4me3, and meiotic recombination hotspot activity. The observed allelic variation alters the DNA-binding sequence specificity of the protein, resulting in distinct meiotic recombination hotspots amongst individuals and populations. Multiple alternate alleles of this gene have been described. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0044296086).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM9 | NM_020227.4 | c.2284C>G | p.His762Asp | missense_variant | 11/11 | ENST00000296682.4 | NP_064612.2 | |
PRDM9 | NM_001376900.1 | c.2284C>G | p.His762Asp | missense_variant | 11/11 | NP_001363829.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM9 | ENST00000296682.4 | c.2284C>G | p.His762Asp | missense_variant | 11/11 | 1 | NM_020227.4 | ENSP00000296682.4 | ||
PRDM9 | ENST00000502755.6 | c.2284C>G | p.His762Asp | missense_variant | 11/11 | 4 | ENSP00000425471.2 |
Frequencies
GnomAD3 genomes Cov.: 11
GnomAD3 genomes
Cov.:
11
GnomAD3 exomes AF: 0.00000870 AC: 2AN: 229848Hom.: 0 AF XY: 0.0000159 AC XY: 2AN XY: 125628
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000941 AC: 13AN: 1381014Hom.: 0 Cov.: 37 AF XY: 0.0000160 AC XY: 11AN XY: 686948
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome Cov.: 11
GnomAD4 genome
Cov.:
11
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.0632);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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