rs2287696

chr5-123124637-G-Achr5-123124637-G-T

Variant summary

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

The NM_001136239.4(PRDM6):c.900+24676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,108 control chromosomes in the GnomAD database, including 2,481 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 0.16 (2481 hom., cov: 33)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594

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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM6	NM_001136239.4	c.900+24676G>A		intron_variant		ENST00000407847.5
PRDM6	XM_011543726.4	c.300+24676G>A		intron_variant
PRDM6	XM_047417878.1	c.900+24676G>A		intron_variant
PRDM6	XR_001742346.2	n.1194+24676G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5	c.900+24676G>A		intron_variant		5	NM_001136239.4	P1
PRDM6	ENST00000434521.1	c.217+24676G>A		intron_variant, NMD_transcript_variant		2
PRDM6	ENST00000464424.1	n.216+24676G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24929 AN: 151990 Hom.: 2477 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.164 AC: 24953 AN: 152108 Hom.: 2481 Cov.: 33 AF XY: 0.170 AC XY: 12657 AN XY: 74356

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.156

Alfa AF: 0.132 Hom.: 721

Bravo AF: 0.164

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	15
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2287696; hg19: chr5-122460332;