5-123090182-C-T

Variant names:

• chr5-123090182-C-T
• rs537520863
• NM_001136239.4:c.168C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001136239.4(PRDM6):​c.168C>T​(p.Pro56Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P56P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRDM6 NM_001136239.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 0 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-AS1 (HGNC:55869): (PRDM6 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-2.59 with no splicing effect.

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.168C>T	p.Pro56Pro	synonymous	Exon 2 of 8	NP_001129711.1	Q9NQX0-3
	PRDM6-AS1	NR_146771.1		n.135G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM6	ENST00000407847.5	TSL:5 MANE Select	c.168C>T	p.Pro56Pro	synonymous	Exon 2 of 8	ENSP00000384725.3	Q9NQX0-3
	PRDM6	ENST00000890813.1		c.168C>T	p.Pro56Pro	synonymous	Exon 1 of 7	ENSP00000560872.1
	PRDM6-AS1	ENST00000458103.3	TSL:2	n.118G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1325148 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 653244

African (AFR) AF: 0.00 AC: 0 AN: 26420

American (AMR) AF: 0.00 AC: 0 AN: 26826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22662

East Asian (EAS) AF: 0.00 AC: 0 AN: 28878

South Asian (SAS) AF: 0.00 AC: 0 AN: 72108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045342

Other (OTH) AF: 0.00 AC: 0 AN: 54766

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.8
DANN	Benign	0.97
PhyloP100		-2.6

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: rs537520863; hg19: chr5-122425877;