Variant chr5-23510049-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020227.4(PRDM9):c.301+44del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 5407 hom., cov: 0)

Exomes 𝑓: 0.33 ( 648 hom. )

Failed GnomAD Quality Control

Consequence

PRDM9
NM_020227.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-23510049-AT-A is Benign according to our data. Variant chr5-23510049-AT-A is described in ClinVar as [Benign]. Clinvar id is 1249566.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 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.301+44del		intron_variant		ENST00000296682.4
PRDM9	NM_001376900.1 linkuse as main transcript	c.301+44del		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
PRDM9	ENST00000296682.4 linkuse as main transcript	c.301+44del	intron_variant	1	NM_020227.4	P1
PRDM9	ENST00000502755.6 linkuse as main transcript	c.301+44del	intron_variant	4
PRDM9	ENST00000635252.1 linkuse as main transcript	c.124+44del	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

37408

AN:

105682

Hom.:

5401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.211

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.332

GnomAD3 exomes

AF:

0.256

AC:

24687

AN:

96360

Hom.:

AF XY:

0.252

AC XY:

12886

AN XY:

51080

show subpopulations

Gnomad AFR exome

AF:

0.278

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.326

AC:

366281

AN:

1122686

Hom.:

648

Cov.:

AF XY:

0.325

AC XY:

181923

AN XY:

560120

show subpopulations

Gnomad4 AFR exome

AF:

0.360

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.326

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.354

AC:

37414

AN:

105674

Hom.:

5407

Cov.:

AF XY:

0.349

AC XY:

17230

AN XY:

49318

show subpopulations

Gnomad4 AFR

AF:

0.477

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.333

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 submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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