rs459743

Variant names:

• chr5-123161237-T-C
• rs459743
• NM_001136239.4:c.1153+1599T>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.1153+1599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,186 control chromosomes in the GnomAD database, including 3,908 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 0.21 (3908 hom., cov: 33)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• 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: 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM6	NM_001136239.4	c.1153+1599T>C		intron_variant	Intron 5 of 7	ENST00000407847.5	NP_001129711.1
PRDM6	XM_011543726.4	c.553+1599T>C		intron_variant	Intron 4 of 6		XP_011542028.1
PRDM6	XM_047417878.1	c.901-9529T>C		intron_variant	Intron 3 of 3		XP_047273834.1
PRDM6	XR_001742346.2	n.1447+1599T>C		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM6	ENST00000407847.5	c.1153+1599T>C		intron_variant	Intron 5 of 7	5	NM_001136239.4	ENSP00000384725.3
PRDM6	ENST00000434521.1	n.217-9529T>C		intron_variant	Intron 1 of 2	2		ENSP00000390919.1
PRDM6	ENST00000464424.1	n.344+5226T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31571 AN: 152068 Hom.: 3899 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0186

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.208 AC: 31603 AN: 152186 Hom.: 3908 Cov.: 33 AF XY: 0.202 AC XY: 15058 AN XY: 74402

African (AFR) AF: 0.341 AC: 14157 AN: 41494

American (AMR) AF: 0.135 AC: 2071 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5192

South Asian (SAS) AF: 0.112 AC: 539 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1915 AN: 10598

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11712 AN: 68006

Other (OTH) AF: 0.199 AC: 420 AN: 2112

Alfa AF: 0.179 Hom.: 11389

Bravo AF: 0.208

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		0.39
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: rs459743; hg19: chr5-122496931;