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GeneBe

5-23509490-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_020227.4(PRDM9):c.90C>T(p.Asp30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,614,120 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 187 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 139 hom. )

Consequence

PRDM9
NM_020227.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.416
Variant links:
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 Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-23509490-C-T is Benign according to our data. Variant chr5-23509490-C-T is described in ClinVar as [Benign]. Clinvar id is 769646.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.416 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRDM9NM_020227.4 linkuse as main transcriptc.90C>T p.Asp30= synonymous_variant 3/11 ENST00000296682.4
PRDM9NM_001376900.1 linkuse as main transcriptc.90C>T p.Asp30= synonymous_variant 3/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRDM9ENST00000296682.4 linkuse as main transcriptc.90C>T p.Asp30= synonymous_variant 3/111 NM_020227.4 P1
PRDM9ENST00000502755.6 linkuse as main transcriptc.90C>T p.Asp30= synonymous_variant 3/114
PRDM9ENST00000635252.1 linkuse as main transcriptc.17-430C>T intron_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0264
AC:
4009
AN:
152128
Hom.:
184
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0914
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.0182
GnomAD3 exomes
AF:
0.00686
AC:
1713
AN:
249576
Hom.:
80
AF XY:
0.00526
AC XY:
712
AN XY:
135400
show subpopulations
Gnomad AFR exome
AF:
0.0956
Gnomad AMR exome
AF:
0.00521
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000291
Gnomad OTH exome
AF:
0.00247
GnomAD4 exome
AF:
0.00265
AC:
3880
AN:
1461874
Hom.:
139
Cov.:
32
AF XY:
0.00230
AC XY:
1676
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0907
Gnomad4 AMR exome
AF:
0.00610
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000301
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000137
Gnomad4 OTH exome
AF:
0.00601
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0265
AC:
4032
AN:
152246
Hom.:
187
Cov.:
32
AF XY:
0.0258
AC XY:
1920
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0917
Gnomad4 AMR
AF:
0.0110
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.0180
Alfa
AF:
0.00671
Hom.:
13
Bravo
AF:
0.0303
Asia WGS
AF:
0.00722
AC:
25
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000533

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
9.1
Dann
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7714612; hg19: chr5-23509599; COSMIC: COSV104393117; API