5-123090166-A-AGCC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_001136239.4(PRDM6):c.165_167dup(p.Pro58dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,489,220 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (7 hom.)
• Consequence: PRDM6 NM_001136239.4 inframe_insertion
• Clinical Significance: 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 -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001136239.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 5-123090166-A-AGCC is Benign according to our data. Variant chr5-123090166-A-AGCC is described in ClinVar as [Benign]. Clinvar id is 3033717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 164 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM6	NM_001136239.4	c.165_167dup	p.Pro58dup	inframe_insertion	2/8	ENST00000407847.5
PRDM6-AS1	NR_146771.1	n.150_151insGGC		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1	c.165_167dup	p.Pro58dup	inframe_insertion	2/4
PRDM6	XR_001742346.2	n.459_461dup		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5	c.165_167dup	p.Pro58dup	inframe_insertion	2/8	5	NM_001136239.4	P1
PRDM6-AS1	ENST00000458103.2	n.133_134insGGC		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 164 AN: 148452 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000995

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000463

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00520

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00138 AC: 120 AN: 87172 Hom.: 3 AF XY: 0.00160 AC XY: 79 AN XY: 49466

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00539

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00169 AC: 2259 AN: 1340654 Hom.: 7 Cov.: 38 AF XY: 0.00180 AC XY: 1189 AN XY: 660798

Gnomad4 AFR exome AF: 0.000873

Gnomad4 AMR exome AF: 0.000106

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000306

Gnomad4 SAS exome AF: 0.00621

Gnomad4 FIN exome AF: 0.0000222

Gnomad4 NFE exome AF: 0.00160

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00110 AC: 164 AN: 148566 Hom.: 1 Cov.: 32 AF XY: 0.000976 AC XY: 71 AN XY: 72738

Gnomad4 AFR AF: 0.000992

Gnomad4 AMR AF: 0.000462

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00521

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000956

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PRDM6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 12, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;