Variant 5-23510049-ATT-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+43_301+44del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,199,738 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 25 hom., cov: 0)

Exomes 𝑓: 0.13 ( 12 hom. )

Consequence

PRDM9
NM_020227.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

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 -10 ACMG points.

BP6

Variant 5-23510049-ATT-A is Benign according to our data. Variant chr5-23510049-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1295150.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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+43_301+44del		intron_variant		ENST00000296682.4
PRDM9	NM_001376900.1 linkuse as main transcript	c.301+43_301+44del		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
PRDM9	ENST00000296682.4 linkuse as main transcript	c.301+43_301+44del	intron_variant	1	NM_020227.4	P1
PRDM9	ENST00000502755.6 linkuse as main transcript	c.301+43_301+44del	intron_variant	4
PRDM9	ENST00000635252.1 linkuse as main transcript	c.124+43_124+44del	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

2743

AN:

105696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.00839

Gnomad FIN

AF:

0.00623

Gnomad MID

AF:

0.0324

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0338

GnomAD3 exomes

AF:

0.138

AC:

13301

AN:

96360

Hom.:

AF XY:

0.133

AC XY:

6796

AN XY:

51080

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0631

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.129

AC:

141083

AN:

1094050

Hom.:

AF XY:

0.128

AC XY:

69873

AN XY:

544950

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.0260

AC:

2743

AN:

105688

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1240

AN XY:

49314

show subpopulations

Gnomad4 AFR

AF:

0.0476

Gnomad4 AMR

AF:

0.0220

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.0360

Gnomad4 SAS

AF:

0.00846

Gnomad4 FIN

AF:

0.00623

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0335

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 21, 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