NM_020227.4:c.301+67A>G

Variant names:

• chr5-23510094-A-G
• rs2973615
• NM_020227.4:c.301+67A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020227.4(PRDM9):​c.301+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,451,960 control chromosomes in the GnomAD database, including 671,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (66328 hom., cov: 19)
  • Exomes 𝑓: 0.96 (605235 hom.)
• Consequence: PRDM9 NM_020227.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 5-23510094-A-G is Benign according to our data. Variant chr5-23510094-A-G is described in ClinVar as Benign. ClinVar VariationId is 1252878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

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+67A>G		intron	N/A	NP_064612.2	Q9NQV7
	PRDM9	NM_001376900.1		c.301+67A>G		intron	N/A	NP_001363829.1	Q9NQV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM9	ENST00000296682.4	TSL:1 MANE Select	c.301+67A>G		intron	N/A	ENSP00000296682.4	Q9NQV7
	PRDM9	ENST00000502755.6	TSL:4	c.301+67A>G		intron	N/A	ENSP00000425471.2	Q9NQV7
	PRDM9	ENST00000635252.1	TSL:5	c.124+67A>G		intron	N/A	ENSP00000489227.1	A0A0U1RQY2

Frequencies

GnomAD3 genomes AF: 0.957 AC: 138361 AN: 144514 Hom.: 66295 Cov.: 19

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.964

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.974

GnomAD4 exome AF: 0.962 AC: 1257342 AN: 1307374 Hom.: 605235 AF XY: 0.962 AC XY: 626871 AN XY: 651572

African (AFR) AF: 0.942 AC: 27666 AN: 29354

American (AMR) AF: 0.989 AC: 35398 AN: 35792

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 23040 AN: 23578

East Asian (EAS) AF: 0.801 AC: 28349 AN: 35380

South Asian (SAS) AF: 0.969 AC: 75943 AN: 78404

European-Finnish (FIN) AF: 0.978 AC: 46755 AN: 47830

Middle Eastern (MID) AF: 0.972 AC: 4911 AN: 5054

European-Non Finnish (NFE) AF: 0.965 AC: 963334 AN: 997884

Other (OTH) AF: 0.960 AC: 51946 AN: 54098

GnomAD4 genome AF: 0.957 AC: 138430 AN: 144586 Hom.: 66328 Cov.: 19 AF XY: 0.958 AC XY: 66837 AN XY: 69778

African (AFR) AF: 0.945 AC: 36405 AN: 38508

American (AMR) AF: 0.980 AC: 13930 AN: 14208

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3362 AN: 3438

East Asian (EAS) AF: 0.818 AC: 3894 AN: 4762

South Asian (SAS) AF: 0.959 AC: 4305 AN: 4488

European-Finnish (FIN) AF: 0.981 AC: 8944 AN: 9116

Middle Eastern (MID) AF: 0.968 AC: 271 AN: 280

European-Non Finnish (NFE) AF: 0.965 AC: 64535 AN: 66906

Other (OTH) AF: 0.973 AC: 1918 AN: 1972

Alfa AF: 0.949 Hom.: 7368

Asia WGS AF: 0.916 AC: 3183 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.37
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2973615; hg19: chr5-23510203;