Variant rs56256550 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020227.4(PRDM9):c.2190C>A(p.Ser730Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRDM9
NM_020227.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.61

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16019985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM9	NM_020227.4 linkuse as main transcript	c.2190C>A	p.Ser730Arg	missense_variant	11/11	ENST00000296682.4	NP_064612.2
PRDM9	NM_001376900.1 linkuse as main transcript	c.2190C>A	p.Ser730Arg	missense_variant	11/11		NP_001363829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM9	ENST00000296682.4 linkuse as main transcript	c.2190C>A	p.Ser730Arg	missense_variant	11/11	1	NM_020227.4	ENSP00000296682	P1
PRDM9	ENST00000502755.6 linkuse as main transcript	c.2190C>A	p.Ser730Arg	missense_variant	11/11	4		ENSP00000425471

Frequencies

GnomAD3 genomes

AF:

0.000722

AC:

AN:

113640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000847

Gnomad ASJ

AF:

0.000674

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.000611

Gnomad FIN

AF:

0.000121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000337

Gnomad OTH

AF:

0.000654

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

235942

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000309

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000167

AC:

AN:

1380688

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

685962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000694

Gnomad4 AMR exome

AF:

0.0000258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000880

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000122

Gnomad4 OTH exome

AF:

0.0000729

GnomAD4 genome

AF:

0.000739

AC:

AN:

113716

Hom.:

Cov.:

AF XY:

0.000754

AC XY:

AN XY:

55674

show subpopulations

Gnomad4 AFR

AF:

0.00186

Gnomad4 AMR

AF:

0.000846

Gnomad4 ASJ

AF:

0.000674

Gnomad4 EAS

AF:

0.000776

Gnomad4 SAS

AF:

0.000611

Gnomad4 FIN

AF:

0.000121

Gnomad4 NFE

AF:

0.000337

Gnomad4 OTH

AF:

0.000645

Alfa

AF:

0.0138

Hom.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.59

DANN

Benign

0.79

DEOGEN2

Benign

0.17

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.033

M_CAP

Benign

0.0021

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.44

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.059

Sift

Benign

0.047

Sift4G

Benign

0.072

Polyphen

0.89

Vest4

0.13

MutPred

0.65

Gain of MoRF binding (P = 0.0176);

MVP

0.048

MPC

0.18

ClinPred

0.22

GERP RS

-5.6

Varity_R

0.27

gMVP

0.021

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over