5-123113955-T-C

Variant names:

• chr5-123113955-T-C
• rs570682
• NM_001136239.4:c.900+13994T>C

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+13994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,186 control chromosomes in the GnomAD database, including 50,654 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 (50654 hom., cov: 32)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4	c.900+13994T>C		intron_variant	Intron 3 of 7	ENST00000407847.5	NP_001129711.1
PRDM6	XM_011543726.4	c.300+13994T>C		intron_variant	Intron 2 of 6		XP_011542028.1
PRDM6	XM_047417878.1	c.900+13994T>C		intron_variant	Intron 3 of 3		XP_047273834.1
PRDM6	XR_001742346.2	n.1194+13994T>C		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5	c.900+13994T>C		intron_variant	Intron 3 of 7	5	NM_001136239.4	ENSP00000384725.3
PRDM6	ENST00000434521.1	n.216+13994T>C		intron_variant	Intron 1 of 2	2		ENSP00000390919.1
PRDM6	ENST00000464424.1	n.216+13994T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123707 AN: 152068 Hom.: 50627 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.813 AC: 123788 AN: 152186 Hom.: 50654 Cov.: 32 AF XY: 0.809 AC XY: 60188 AN XY: 74390

African (AFR) AF: 0.856 AC: 35566 AN: 41538

American (AMR) AF: 0.789 AC: 12070 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2858 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2746 AN: 5164

South Asian (SAS) AF: 0.767 AC: 3690 AN: 4808

European-Finnish (FIN) AF: 0.760 AC: 8043 AN: 10584

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56163 AN: 68012

Other (OTH) AF: 0.825 AC: 1743 AN: 2112

Alfa AF: 0.821 Hom.: 216090

Bravo AF: 0.816

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.83
DANN	Benign	0.64
PhyloP100		-0.44
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: rs570682; hg19: chr5-122449650;