Genetic Variant NM_020227.4:c.301+35_301+44delTTTTTTTTTT (chr5-23510049-ATTTTTTTTTT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020227.4(PRDM9):c.301+35_301+44delTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,252,546 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000095 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

PRDM9
NM_020227.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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+35_301+44delTTTTTTTTTT		intron	N/A	NP_064612.2	Q9NQV7
	PRDM9	NM_001376900.1		c.301+35_301+44delTTTTTTTTTT		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+23_301+32delTTTTTTTTTT	intron	N/A	ENSP00000296682.4	Q9NQV7
PRDM9	ENST00000502755.6	TSL:4	c.301+23_301+32delTTTTTTTTTT	intron	N/A	ENSP00000425471.2	Q9NQV7
PRDM9	ENST00000635252.1	TSL:5	c.124+23_124+32delTTTTTTTTTT	intron	N/A	ENSP00000489227.1	A0A0U1RQY2

Frequencies

GnomAD3 genomes

AF:

0.00000946

AC:

AN:

105722

Hom.:

Cov.:

show subpopulations

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:

0.0000182

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000262

AC:

AN:

1146824

Hom.:

AF XY:

0.00000523

AC XY:

AN XY:

573212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25126

American (AMR)

AF:

0.00

AC:

AN:

29722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20198

East Asian (EAS)

AF:

0.0000314

AC:

AN:

31826

South Asian (SAS)

AF:

0.00

AC:

AN:

69764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4204

European-Non Finnish (NFE)

AF:

0.00000228

AC:

AN:

878278

Other (OTH)

AF:

0.00

AC:

AN:

47310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000946

AC:

AN:

105722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25324

American (AMR)

AF:

0.00

AC:

AN:

9344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2882

East Asian (EAS)

AF:

0.00

AC:

AN:

3650

South Asian (SAS)

AF:

0.00

AC:

AN:

2978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

54812

Other (OTH)

AF:

0.00

AC:

AN:

1426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over