5-123090181-C-CG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001136239.4(PRDM6):c.167_168insG(p.Pro58AlafsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,487,364 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P56P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 33)
  • Exomes 𝑓: 0.00091 (21 hom.)
• Consequence: PRDM6 NM_001136239.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.59

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 5-123090181-C-CG is Benign according to our data. Variant chr5-123090181-C-CG is described in ClinVar as [Benign]. Clinvar id is 768029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1692/151936) while in subpopulation AFR AF= 0.0387 (1608/41498). AF 95% confidence interval is 0.0372. There are 32 homozygotes in gnomad4. There are 768 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1693 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM6	NM_001136239.4	c.167_168insG	p.Pro58AlafsTer6	frameshift_variant	2/8	ENST00000407847.5
PRDM6-AS1	NR_146771.1	n.135_136insC		non_coding_transcript_exon_variant	1/2
PRDM6	XM_047417878.1	c.167_168insG	p.Pro58AlafsTer6	frameshift_variant	2/4
PRDM6	XR_001742346.2	n.461_462insG		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM6	ENST00000407847.5	c.167_168insG	p.Pro58AlafsTer6	frameshift_variant	2/8	5	NM_001136239.4	P1
PRDM6-AS1	ENST00000458103.2	n.118_119insC		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1693 AN: 151828 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00912

GnomAD3 exomes AF: 0.000119 AC: 10 AN: 84056 Hom.: 0 AF XY: 0.000105 AC XY: 5 AN XY: 47666

Gnomad AFR exome AF: 0.00797

Gnomad AMR exome AF: 0.000133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000427

GnomAD4 exome AF: 0.000914 AC: 1220 AN: 1335428 Hom.: 21 Cov.: 42 AF XY: 0.000784 AC XY: 516 AN XY: 658028

Gnomad4 AFR exome AF: 0.0389

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000692

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000313

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.0111 AC: 1692 AN: 151936 Hom.: 32 Cov.: 33 AF XY: 0.0103 AC XY: 768 AN XY: 74296

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.00387

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00902

Alfa AF: 0.000283 Hom.: 0

Asia WGS AF: 0.000291 AC: 1 AN: 3450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs768810414; hg19: chr5-122425876;