5-23510212-G-T

Position:

• chr5-23510212-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020227.4(PRDM9):​c.301+185G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,430 control chromosomes in the GnomAD database, including 3,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3664 hom., cov: 28)
• Consequence: PRDM9 NM_020227.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.809

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 5-23510212-G-T is Benign according to our data. Variant chr5-23510212-G-T is described in ClinVar as [Benign]. Clinvar id is 1242393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM9	NM_020227.4	c.301+185G>T		intron_variant		ENST00000296682.4
PRDM9	NM_001376900.1	c.301+185G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM9	ENST00000296682.4	c.301+185G>T		intron_variant		1	NM_020227.4	P1
PRDM9	ENST00000502755.6	c.301+185G>T		intron_variant		4
PRDM9	ENST00000635252.1	c.124+185G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32021 AN: 151312 Hom.: 3649 Cov.: 28

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32057 AN: 151430 Hom.: 3664 Cov.: 28 AF XY: 0.216 AC XY: 15979 AN XY: 73928

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0986 Hom.: 139

Bravo AF: 0.221

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.50

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: rs7718359; hg19: chr5-23510321;