dbSNP rs768810414: PRDM6:p.Pro58AlafsTer6 (chr5-123090181-C-CG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.59

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1692 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.167_168insG	p.Pro58AlafsTer6	frameshift	Exon 2 of 8	NP_001129711.1	Q9NQX0-3
	PRDM6-AS1	NR_146771.1		n.135_136insC		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.167_168insG	p.Pro58AlafsTer6	frameshift	Exon 2 of 8	ENSP00000384725.3	Q9NQX0-3
PRDM6	ENST00000890813.1		c.167_168insG	p.Pro58AlafsTer6	frameshift	Exon 1 of 7	ENSP00000560872.1
PRDM6-AS1	ENST00000458103.3	TSL:2	n.118_119insC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1693

AN:

151828

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000119

AC:

AN:

84056

AF XY:

0.000105

show subpopulations

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 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.:

Cov.:

AF XY:

0.000784

AC XY:

516

AN XY:

658028

show subpopulations

African (AFR)

AF:

0.0389

AC:

1025

AN:

26346

American (AMR)

AF:

0.00141

AC:

AN:

26982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22846

East Asian (EAS)

AF:

0.00

AC:

AN:

28886

South Asian (SAS)

AF:

0.0000692

AC:

AN:

72264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44018

Middle Eastern (MID)

AF:

0.00138

AC:

AN:

4352

European-Non Finnish (NFE)

AF:

0.0000313

AC:

AN:

1054666

Other (OTH)

AF:

0.00205

AC:

113

AN:

55068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.0111

AC:

1692

AN:

151936

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

768

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0387

AC:

1608

AN:

41498

American (AMR)

AF:

0.00387

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67898

Other (OTH)

AF:

0.00902

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

146

220

293

366

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:

0.000283

Hom.:

Asia WGS

AF:

0.000291

AC:

AN:

3450

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

PRDM6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.6

Mutation Taster

=133/67

disease causing (fs/PTC)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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