chr5-23510049-A-ATTT

Variant names:

• chr5-23510049-A-ATTT
• rs34033521
• NM_020227.4:c.301+42_301+44dupTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_020227.4(PRDM9):​c.301+42_301+44dupTTT 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 0.000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00051 (0 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM9	NM_020227.4	c.301+42_301+44dupTTT		intron_variant	Intron 4 of 10	ENST00000296682.4	NP_064612.2
PRDM9	NM_001376900.1	c.301+42_301+44dupTTT		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+23insTTT		intron_variant	Intron 4 of 10	1	NM_020227.4	ENSP00000296682.4
PRDM9	ENST00000502755.6	c.301+22_301+23insTTT		intron_variant	Intron 4 of 10	4		ENSP00000425471.2
PRDM9	ENST00000635252.1	c.124+22_124+23insTTT		intron_variant	Intron 4 of 10	5		ENSP00000489227.1

Frequencies

GnomAD3 genomes AF: 0.0000662 AC: 7 AN: 105718 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000347

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: 0.00140

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000506 AC: 580 AN: 1145898 Hom.: 0 Cov.: 0 AF XY: 0.000529 AC XY: 303 AN XY: 572768

Gnomad4 AFR exome AF: 0.000279

Gnomad4 AMR exome AF: 0.000909

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.000157

Gnomad4 SAS exome AF: 0.000574

Gnomad4 FIN exome AF: 0.00136

Gnomad4 NFE exome AF: 0.000446

Gnomad4 OTH exome AF: 0.000487

GnomAD4 genome AF: 0.0000662 AC: 7 AN: 105718 Hom.: 0 Cov.: 0 AF XY: 0.0000608 AC XY: 3 AN XY: 49318

Gnomad4 AFR AF: 0.000118

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000182

Gnomad4 OTH AF: 0.00140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;