rs6872465

chr5-123126892-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2323 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM6	NM_001136239.4	c.900+26931C>T		intron_variant		ENST00000407847.5
PRDM6	XM_011543726.4	c.300+26931C>T		intron_variant
PRDM6	XM_047417878.1	c.900+26931C>T		intron_variant
PRDM6	XR_001742346.2	n.1194+26931C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5	c.900+26931C>T		intron_variant		5	NM_001136239.4	P1
PRDM6	ENST00000434521.1	c.217+26931C>T		intron_variant, NMD_transcript_variant		2
PRDM6	ENST00000464424.1	n.216+26931C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.00481

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0241

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.4
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs6872465; hg19: chr5-122462587;