chr5-23522699-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_020227.4(PRDM9):c.696G>C(p.Lys232Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,614,206 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 1 hom. )
Consequence
PRDM9
NM_020227.4 missense
NM_020227.4 missense
Scores
7
7
Clinical Significance
Conservation
PhyloP100: 1.86
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.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008793861).
BP6
?
Variant 5-23522699-G-C is Benign according to our data. Variant chr5-23522699-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052715.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM9 | NM_020227.4 | c.696G>C | p.Lys232Asn | missense_variant | 8/11 | ENST00000296682.4 | |
PRDM9 | NM_001376900.1 | c.696G>C | p.Lys232Asn | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM9 | ENST00000296682.4 | c.696G>C | p.Lys232Asn | missense_variant | 8/11 | 1 | NM_020227.4 | P1 | |
PRDM9 | ENST00000502755.6 | c.696G>C | p.Lys232Asn | missense_variant | 8/11 | 4 | |||
PRDM9 | ENST00000635252.1 | c.519G>C | p.Lys173Asn | missense_variant | 8/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000953 AC: 145AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251274Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135840
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GnomAD4 exome AF: 0.000112 AC: 163AN: 1461870Hom.: 1 Cov.: 32 AF XY: 0.0000976 AC XY: 71AN XY: 727242
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GnomAD4 genome ? AF: 0.000952 AC: 145AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.00101 AC XY: 75AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PRDM9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 02, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
0.97
.;D
Vest4
0.24
MutPred
0.40
.;Loss of ubiquitination at K232 (P = 0.0039);
MVP
0.68
MPC
0.38
ClinPred
T
GERP RS
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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