chr5-123090166-A-AGCCGCCGCC

Variant names:

• chr5-123090166-A-AGCCGCCGCC
• rs563892036
• NM_001136239.4:c.159_167dupGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4 BS2

The NM_001136239.4(PRDM6):​c.159_167dupGCCGCCGCC​(p.Pro54_Pro56dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000671 in 1,340,682 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: PRDM6 NM_001136239.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• 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-AS1 (HGNC:55869): (PRDM6 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001136239.4.
• BS2: High AC in GnomAdExome4 at 9 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.159_167dupGCCGCCGCC	p.Pro54_Pro56dup	disruptive_inframe_insertion	Exon 2 of 8	NP_001129711.1	Q9NQX0-3
	PRDM6-AS1	NR_146771.1		n.142_150dupGGCGGCGGC		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.159_167dupGCCGCCGCC	p.Pro54_Pro56dup	disruptive_inframe_insertion	Exon 2 of 8	ENSP00000384725.3	Q9NQX0-3
	PRDM6	ENST00000890813.1		c.159_167dupGCCGCCGCC	p.Pro54_Pro56dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000560872.1
	PRDM6-AS1	ENST00000458103.3	TSL:2	n.125_133dupGGCGGCGGC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000671 AC: 9 AN: 1340682 Hom.: 0 Cov.: 38 AF XY: 0.00000605 AC XY: 4 AN XY: 660814

African (AFR) AF: 0.0000759 AC: 2 AN: 26350

American (AMR) AF: 0.00 AC: 0 AN: 28376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23196

East Asian (EAS) AF: 0.0000340 AC: 1 AN: 29378

South Asian (SAS) AF: 0.0000273 AC: 2 AN: 73286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4564

European-Non Finnish (NFE) AF: 0.00000284 AC: 3 AN: 1055250

Other (OTH) AF: 0.0000181 AC: 1 AN: 55298

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=69/31	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs563892036; hg19: chr5-122425861;