Genetic Variant PRDM9:c.301+67A>C (chr5-23510094-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020227.4(PRDM9):c.301+67A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRDM9
NM_020227.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM9	NM_020227.4	MANE Select	c.301+67A>C		intron	N/A	NP_064612.2	Q9NQV7
	PRDM9	NM_001376900.1		c.301+67A>C		intron	N/A	NP_001363829.1	Q9NQV7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRDM9	ENST00000296682.4	TSL:1 MANE Select	c.301+67A>C	intron	N/A	ENSP00000296682.4	Q9NQV7
PRDM9	ENST00000502755.6	TSL:4	c.301+67A>C	intron	N/A	ENSP00000425471.2	Q9NQV7
PRDM9	ENST00000635252.1	TSL:5	c.124+67A>C	intron	N/A	ENSP00000489227.1	A0A0U1RQY2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144558

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1307732

Hom.:

AF XY:

0.00

AC XY:

AN XY:

651738

African (AFR)

AF:

0.00

AC:

AN:

29360

American (AMR)

AF:

0.00

AC:

AN:

35794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23580

East Asian (EAS)

AF:

0.00

AC:

AN:

35426

South Asian (SAS)

AF:

0.00

AC:

AN:

78412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5054

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

998146

Other (OTH)

AF:

0.00

AC:

AN:

54124

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

144558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69706

African (AFR)

AF:

0.00

AC:

AN:

38434

American (AMR)

AF:

0.00

AC:

AN:

14190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4786

South Asian (SAS)

AF:

0.00

AC:

AN:

4498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66924

Other (OTH)

AF:

0.00

AC:

AN:

1962

Alfa

AF:

0.00

Hom.:

7368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.50

(source)

DANN

Benign

0.35

PhyloP100

-1.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over