Genetic Variant PRDM6:p.Pro55_Pro56dup (chr5-123090166-A-AGCCGCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_001136239.4(PRDM6):c.162_167dupGCCGCC(p.Pro55_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 0.00815 in 1,488,890 control chromosomes in the GnomAD database, including 67 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P56P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0070 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 62 hom. )

Consequence

PRDM6
NM_001136239.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

Publications

2 publications found

Variant links:

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 links:

PRDM6-AS1 (HGNC:55869): (PRDM6 antisense RNA 1)

PRDM6-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2655659.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1043 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.162_167dupGCCGCC	p.Pro55_Pro56dup	disruptive_inframe_insertion	Exon 2 of 8	NP_001129711.1	Q9NQX0-3
	PRDM6-AS1	NR_146771.1		n.145_150dupGGCGGC		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM6	ENST00000407847.5	TSL:5 MANE Select	c.162_167dupGCCGCC	p.Pro55_Pro56dup	disruptive_inframe_insertion	Exon 2 of 8	ENSP00000384725.3	Q9NQX0-3
PRDM6	ENST00000890813.1		c.162_167dupGCCGCC	p.Pro55_Pro56dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000560872.1
PRDM6-AS1	ENST00000458103.3	TSL:2	n.128_133dupGGCGGC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00703

AC:

1044

AN:

148450

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00275

AC:

240

AN:

87172

AF XY:

0.00293

show subpopulations

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 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.:

Cov.:

AF XY:

0.00806

AC XY:

5322

AN XY:

660634

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

26348

American (AMR)

AF:

0.00427

AC:

121

AN:

28366

Ashkenazi Jewish (ASJ)

AF:

0.00850

AC:

197

AN:

23188

East Asian (EAS)

AF:

0.000579

AC:

AN:

29378

South Asian (SAS)

AF:

0.00173

AC:

127

AN:

73266

European-Finnish (FIN)

AF:

0.00534

AC:

240

AN:

44968

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

4560

European-Non Finnish (NFE)

AF:

0.00931

AC:

9824

AN:

1054968

Other (OTH)

AF:

0.00827

AC:

457

AN:

55284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

552

1104

1656

2208

2760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

388

776

1164

1552

1940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00702

AC:

1043

AN:

148564

Hom.:

Cov.:

AF XY:

0.00664

AC XY:

483

AN XY:

72736

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

38302

American (AMR)

AF:

0.0108

AC:

164

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.000780

AC:

AN:

5128

South Asian (SAS)

AF:

0.00187

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00398

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0104

AC:

703

AN:

67898

Other (OTH)

AF:

0.00870

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

111

166

222

277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00159

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=69/31

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over