Genetic Variant PDE4DIP:p.Lys439Lys (chr1-148962565-A-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001395426.1(PDE4DIP):c.1317A>G(p.Lys439Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 16)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

PDE4DIP
NM_001395426.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.106

Publications

3 publications found

Variant links:

Genes affected

PDE4DIP (HGNC:15580): (phosphodiesterase 4D interacting protein) The protein encoded by this gene serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

PDE4DIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-148962565-A-G is Benign according to our data. Variant chr1-148962565-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2639075.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.106 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395426.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE4DIP	NM_001395426.1	MANE Select	c.1317A>G	p.Lys439Lys	synonymous	Exon 12 of 47	NP_001382355.1	A0A8Q3SI83
PDE4DIP	NM_001395297.1		c.1608A>G	p.Lys536Lys	synonymous	Exon 5 of 40	NP_001382226.1
PDE4DIP	NM_001350520.2		c.1608A>G	p.Lys536Lys	synonymous	Exon 5 of 40	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE4DIP	ENST00000695795.1	MANE Select	c.1317A>G	p.Lys439Lys	synonymous	Exon 12 of 47	ENSP00000512175.1	A0A8Q3SI83
PDE4DIP	ENST00000369356.8	TSL:1	c.1119A>G	p.Lys373Lys	synonymous	Exon 9 of 44	ENSP00000358363.4	Q5VU43-4
PDE4DIP	ENST00000369354.7	TSL:1	c.1119A>G	p.Lys373Lys	synonymous	Exon 9 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

148

AN:

127330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000327

Gnomad OTH

AF:

0.000630

GnomAD2 exomes

AF:

0.000254

AC:

AN:

251478

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.000347

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:

0.000326

GnomAD4 exome

AF:

0.000150

AC:

AN:

501478

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

267082

show subpopulations

African (AFR)

AF:

0.00326

AC:

AN:

14402

American (AMR)

AF:

0.000595

AC:

AN:

25214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15530

East Asian (EAS)

AF:

0.00

AC:

AN:

33520

South Asian (SAS)

AF:

0.00

AC:

AN:

52240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33476

Middle Eastern (MID)

AF:

0.000405

AC:

AN:

2472

European-Non Finnish (NFE)

AF:

0.00000675

AC:

AN:

296432

Other (OTH)

AF:

0.000355

AC:

AN:

28192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00116

AC:

148

AN:

127452

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

60568

show subpopulations

African (AFR)

AF:

0.00428

AC:

139

AN:

32486

American (AMR)

AF:

0.000496

AC:

AN:

12086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3154

East Asian (EAS)

AF:

0.00

AC:

AN:

4480

South Asian (SAS)

AF:

0.00

AC:

AN:

3230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000327

AC:

AN:

61120

Other (OTH)

AF:

0.000622

AC:

AN:

1608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000135

Hom.:

Bravo

AF:

0.00128

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.9

(source)

DANN

Benign

0.58

PhyloP100

0.11

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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