5-123090166-A-AGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_001136239.4(PRDM6):c.162_167dup(p.Pro58_Pro59dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 1,488,890 control chromosomes in the GnomAD database, including 67 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (62 hom.)
• Consequence: PRDM6 NM_001136239.4 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001136239.4.
• BP6: Variant 5-123090166-A-AGCCGCC is Benign according to our data. Variant chr5-123090166-A-AGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 2655659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1044 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM6	NM_001136239.4	c.162_167dup	p.Pro58_Pro59dup	inframe_insertion	2/8	ENST00000407847.5
PRDM6-AS1	NR_146771.1	n.150_151insGGCGGC		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1	c.162_167dup	p.Pro58_Pro59dup	inframe_insertion	2/4
PRDM6	XR_001742346.2	n.456_461dup		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5	c.162_167dup	p.Pro58_Pro59dup	inframe_insertion	2/8	5	NM_001136239.4	P1
PRDM6-AS1	ENST00000458103.2	n.133_134insGGCGGC		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1044 AN: 148450 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000778

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00398

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00880

GnomAD3 exomes AF: 0.00275 AC: 240 AN: 87172 Hom.: 2 AF XY: 0.00293 AC XY: 145 AN XY: 49466

Gnomad AFR exome AF: 0.00104

Gnomad AMR exome AF: 0.00137

Gnomad ASJ exome AF: 0.00323

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000788

Gnomad FIN exome AF: 0.00275

Gnomad NFE exome AF: 0.00481

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00828 AC: 11093 AN: 1340326 Hom.: 62 Cov.: 38 AF XY: 0.00806 AC XY: 5322 AN XY: 660634

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00427

Gnomad4 ASJ exome AF: 0.00850

Gnomad4 EAS exome AF: 0.000579

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.00534

Gnomad4 NFE exome AF: 0.00931

Gnomad4 OTH exome AF: 0.00827

GnomAD4 genome AF: 0.00702 AC: 1043 AN: 148564 Hom.: 5 Cov.: 32 AF XY: 0.00664 AC XY: 483 AN XY: 72736

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000780

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00398

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.00870

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

PRDM6: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs563892036; hg19: chr5-122425861;