rs9327287

chr5-123183919-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136239.4(PRDM6):c.1674-3168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,032 control chromosomes in the GnomAD database, including 6,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6625 hom., cov: 32)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728

Genes affected

PRDM6 (HGNC:9350): (PR/SET domain 6) The protein encoded by this gene is a transcriptional repressor and a member of the PRDM family. Family members contain a PR domain and multiple zinc-finger domains. The encoded protein is involved in regulation of vascular smooth muscle cells (VSMC) contractile proteins. Mutations in this gene result in patent ductus arteriosus 3 (PDA3). [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM6	NM_001136239.4	c.1674-3168A>G		intron_variant		ENST00000407847.5
PRDM6	XM_011543726.4	c.1074-3168A>G		intron_variant
PRDM6	XR_001742346.2	n.2085-2906A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5	c.1674-3168A>G		intron_variant		5	NM_001136239.4	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43470 AN: 151914 Hom.: 6616 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.286 AC: 43505 AN: 152032 Hom.: 6625 Cov.: 32 AF XY: 0.288 AC XY: 21378 AN XY: 74300

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.312

Alfa AF: 0.294 Hom.: 4553

Bravo AF: 0.291

Asia WGS AF: 0.455 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.3
Dann	Benign	0.64

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: rs9327287; hg19: chr5-122519613;