Genetic Variant PRDM9:c.301+39_301+44delTTTTTT (chr5-23510049-ATTTTTT-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_020227.4(PRDM9):c.301+39_301+44delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,252,076 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 0.000019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 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 0 ACMG points.

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+39_301+44delTTTTTT		intron	N/A	NP_064612.2	Q9NQV7
	PRDM9	NM_001376900.1		c.301+39_301+44delTTTTTT		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+28delTTTTTT	intron	N/A	ENSP00000296682.4	Q9NQV7
PRDM9	ENST00000502755.6	TSL:4	c.301+23_301+28delTTTTTT	intron	N/A	ENSP00000425471.2	Q9NQV7
PRDM9	ENST00000635252.1	TSL:5	c.124+23_124+28delTTTTTT	intron	N/A	ENSP00000489227.1	A0A0U1RQY2

Frequencies

GnomAD3 genomes

AF:

0.0000189

AC:

AN:

105722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000107

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:

0.000701

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

96360

AF XY:

0.0000392

show subpopulations

Gnomad AFR exome

AF:

0.000163

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000508

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

145

AN:

1146354

Hom.:

AF XY:

0.000129

AC XY:

AN XY:

572960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000398

AC:

AN:

25100

American (AMR)

AF:

0.000202

AC:

AN:

29702

Ashkenazi Jewish (ASJ)

AF:

0.000198

AC:

AN:

20190

East Asian (EAS)

AF:

0.000189

AC:

AN:

31796

South Asian (SAS)

AF:

0.0000717

AC:

AN:

69750

European-Finnish (FIN)

AF:

0.000149

AC:

AN:

40382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4202

European-Non Finnish (NFE)

AF:

0.000110

AC:

AN:

877946

Other (OTH)

AF:

0.000233

AC:

AN:

47286

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

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:

0.0000189

AC:

AN:

105722

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

49318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25324

American (AMR)

AF:

0.000107

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:

0.00

AC:

AN:

54812

Other (OTH)

AF:

0.000701

AC:

AN:

1426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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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5-23510049-ATTTTTTTTTTT-ATTTTT

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