5-123117450-C-T

Variant names:

• chr5-123117450-C-T
• rs555625
• NM_001136239.4:c.900+17489C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136239.4(PRDM6):​c.900+17489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,224 control chromosomes in the GnomAD database, including 62,769 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 0.91 (62769 hom., cov: 32)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• Publications: 2 publications found

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]

PRDM6 Gene-Disease associations (from GenCC):

• familial patent arterial duct

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• patent ductus arteriosus 3

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4	c.900+17489C>T		intron_variant	Intron 3 of 7	ENST00000407847.5	NP_001129711.1
PRDM6	XM_011543726.4	c.300+17489C>T		intron_variant	Intron 2 of 6		XP_011542028.1
PRDM6	XM_047417878.1	c.900+17489C>T		intron_variant	Intron 3 of 3		XP_047273834.1
PRDM6	XR_001742346.2	n.1194+17489C>T		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5	c.900+17489C>T		intron_variant	Intron 3 of 7	5	NM_001136239.4	ENSP00000384725.3
PRDM6	ENST00000434521.1	n.216+17489C>T		intron_variant	Intron 1 of 2	2		ENSP00000390919.1
PRDM6	ENST00000464424.1	n.216+17489C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137891 AN: 152106 Hom.: 62717 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.914

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

GnomAD4 genome AF: 0.907 AC: 138002 AN: 152224 Hom.: 62769 Cov.: 32 AF XY: 0.911 AC XY: 67832 AN XY: 74440

African (AFR) AF: 0.824 AC: 34185 AN: 41482

American (AMR) AF: 0.946 AC: 14475 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3153 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5118 AN: 5186

South Asian (SAS) AF: 0.981 AC: 4728 AN: 4822

European-Finnish (FIN) AF: 0.958 AC: 10163 AN: 10610

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63111 AN: 68032

Other (OTH) AF: 0.914 AC: 1935 AN: 2116

Alfa AF: 0.923 Hom.: 53745

Bravo AF: 0.903

Asia WGS AF: 0.976 AC: 3392 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	9.2
DANN	Benign	0.60
PhyloP100		0.91
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: rs555625; hg19: chr5-122453145;