5-123106932-C-T

Variant names:

• chr5-123106932-C-T
• rs163189
• NM_001136239.4:c.900+6971C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001136239.4(PRDM6):​c.900+6971C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,232 control chromosomes in the GnomAD database, including 50,370 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 0.81 (50370 hom., cov: 33)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136239.4. 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
	PRDM6	NM_001136239.4	MANE Select	c.900+6971C>T		intron	N/A	NP_001129711.1	Q9NQX0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM6	ENST00000407847.5	TSL:5 MANE Select	c.900+6971C>T		intron	N/A	ENSP00000384725.3	Q9NQX0-3
	PRDM6	ENST00000890813.1		c.900+6971C>T		intron	N/A	ENSP00000560872.1
	PRDM6	ENST00000434521.1	TSL:2	n.216+6971C>T		intron	N/A	ENSP00000390919.1	H7BZR2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123325 AN: 152114 Hom.: 50345 Cov.: 33

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.811 AC: 123405 AN: 152232 Hom.: 50370 Cov.: 33 AF XY: 0.806 AC XY: 59947 AN XY: 74406

African (AFR) AF: 0.856 AC: 35551 AN: 41544

American (AMR) AF: 0.783 AC: 11971 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2752 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2735 AN: 5180

South Asian (SAS) AF: 0.728 AC: 3516 AN: 4828

European-Finnish (FIN) AF: 0.764 AC: 8078 AN: 10574

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56201 AN: 68020

Other (OTH) AF: 0.813 AC: 1719 AN: 2114

Alfa AF: 0.820 Hom.: 129803

Bravo AF: 0.814

Asia WGS AF: 0.649 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		3.2
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: rs163189; hg19: chr5-122442627;