NM_020227.4:c.301+44dupT

Variant names:

• chr5-23510049-A-AT
• rs34033521
• NM_020227.4:c.301+44dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020227.4(PRDM9):​c.301+44dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.070 (303 hom., cov: 0)
  • Exomes 𝑓: 0.070 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRDM9 NM_020227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM9	NM_020227.4	c.301+44dupT		intron_variant	Intron 4 of 10	ENST00000296682.4	NP_064612.2
PRDM9	NM_001376900.1	c.301+44dupT		intron_variant	Intron 4 of 10		NP_001363829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM9	ENST00000296682.4	c.301+22_301+23insT		intron_variant	Intron 4 of 10	1	NM_020227.4	ENSP00000296682.4
PRDM9	ENST00000502755.6	c.301+22_301+23insT		intron_variant	Intron 4 of 10	4		ENSP00000425471.2
PRDM9	ENST00000635252.1	c.124+22_124+23insT		intron_variant	Intron 4 of 10	5		ENSP00000489227.1

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 7363 AN: 105676 Hom.: 303 Cov.: 0

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0153

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0836

GnomAD3 exomes AF: 0.0454 AC: 4379 AN: 96360 Hom.: 4 AF XY: 0.0445 AC XY: 2275 AN XY: 51080

Gnomad AFR exome AF: 0.0315

Gnomad AMR exome AF: 0.0520

Gnomad ASJ exome AF: 0.0915

Gnomad EAS exome AF: 0.0276

Gnomad SAS exome AF: 0.0362

Gnomad FIN exome AF: 0.0384

Gnomad NFE exome AF: 0.0465

Gnomad OTH exome AF: 0.0585

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0700 AC: 78697 AN: 1124384 Hom.: 18 Cov.: 0 AF XY: 0.0691 AC XY: 38793 AN XY: 561702

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.0999

Gnomad4 EAS exome AF: 0.0364

Gnomad4 SAS exome AF: 0.0431

Gnomad4 FIN exome AF: 0.0470

Gnomad4 NFE exome AF: 0.0755

Gnomad4 OTH exome AF: 0.0666

GnomAD4 genome AF: 0.0696 AC: 7357 AN: 105668 Hom.: 303 Cov.: 0 AF XY: 0.0664 AC XY: 3273 AN XY: 49304

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.0782

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.0817

Gnomad4 OTH AF: 0.0830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34033521; hg19: chr5-23510158;