Variant 5-23509490-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

PRDM9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.416 with no splicing effect.

BA1

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
PRDM9	NM_020227.4 linkuse as main transcript	c.90C>T	p.Asp30=	synonymous_variant	3/11	ENST00000296682.4
PRDM9	NM_001376900.1 linkuse as main transcript	c.90C>T	p.Asp30=	synonymous_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PRDM9	ENST00000296682.4 linkuse as main transcript	c.90C>T	p.Asp30=	synonymous_variant	3/11	1	NM_020227.4	P1
PRDM9	ENST00000502755.6 linkuse as main transcript	c.90C>T	p.Asp30=	synonymous_variant	3/11	4
PRDM9	ENST00000635252.1 linkuse as main transcript	c.17-430C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4009

AN:

152128

Hom.:

184

Cov.:

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.:

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.:

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

AF:

0.0265

AC:

4032

AN:

152246

Hom.:

187

Cov.:

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.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over