Variant 5-23522263-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020227.4(PRDM9):c.509-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,509,014 control chromosomes in the GnomAD database, including 3,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 353 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3579 hom. )

Consequence

PRDM9
NM_020227.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.540

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-23522263-C-T is Benign according to our data. Variant chr5-23522263-C-T is described in ClinVar as [Benign]. Clinvar id is 1226826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0792 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.509-41C>T		intron_variant		ENST00000296682.4
PRDM9	NM_001376900.1 linkuse as main transcript	c.509-41C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
PRDM9	ENST00000296682.4 linkuse as main transcript	c.509-41C>T	intron_variant	1	NM_020227.4	P1
PRDM9	ENST00000502755.6 linkuse as main transcript	c.509-41C>T	intron_variant	4
PRDM9	ENST00000635252.1 linkuse as main transcript	c.332-41C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8507

AN:

152010

Hom.:

353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0832

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.0282

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0754

Gnomad OTH

AF:

0.0841

GnomAD3 exomes

AF:

0.0567

AC:

14106

AN:

249000

Hom.:

566

AF XY:

0.0575

AC XY:

7769

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0271

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0765

Gnomad OTH exome

AF:

0.0700

GnomAD4 exome

AF:

0.0675

AC:

91592

AN:

1356886

Hom.:

3579

Cov.:

AF XY:

0.0669

AC XY:

45596

AN XY:

681360

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.0569

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0268

Gnomad4 FIN exome

AF:

0.0297

Gnomad4 NFE exome

AF:

0.0754

Gnomad4 OTH exome

AF:

0.0672

GnomAD4 genome

AF:

0.0559

AC:

8499

AN:

152128

Hom.:

353

Cov.:

AF XY:

0.0534

AC XY:

3974

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.0830

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.0282

Gnomad4 NFE

AF:

0.0754

Gnomad4 OTH

AF:

0.0828

Alfa

AF:

0.0746

Hom.:

Bravo

AF:

0.0592

Asia WGS

AF:

0.0120

AC:

AN:

3478

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	GeneDx	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.9

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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