chr5-123126892-C-T

Variant names:

• chr5-123126892-C-T
• rs6872465
• NM_001136239.4:c.900+26931C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001136239.4(PRDM6):​c.900+26931C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,212 control chromosomes in the GnomAD database, including 26 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 0.015 (26 hom., cov: 31)
• Consequence: PRDM6 NM_001136239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0153 (2322/152212) while in subpopulation NFE AF = 0.0183 (1244/68008). AF 95% confidence interval is 0.0174. There are 26 homozygotes in GnomAd4. There are 1080 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2322 AD gene.

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+26931C>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+26931C>T		intron	N/A	ENSP00000384725.3	Q9NQX0-3
	PRDM6	ENST00000890813.1		c.900+26931C>T		intron	N/A	ENSP00000560872.1
	PRDM6	ENST00000434521.1	TSL:2	n.216+26931C>T		intron	N/A	ENSP00000390919.1	H7BZR2

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2323 AN: 152094 Hom.: 25 Cov.: 31

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0153 AC: 2322 AN: 152212 Hom.: 26 Cov.: 31 AF XY: 0.0145 AC XY: 1080 AN XY: 74416

African (AFR) AF: 0.0140 AC: 583 AN: 41530

American (AMR) AF: 0.0130 AC: 198 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4824

European-Finnish (FIN) AF: 0.00481 AC: 51 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0183 AC: 1244 AN: 68008

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

Alfa AF: 0.0157 Hom.: 2

Bravo AF: 0.0158

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.43
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism

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: rs6872465; hg19: chr5-122462587;