Genetic Variant PDE4DIP:p.Ser293Ser (chr1-148953659-C-T) – 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_001395297.1(PDE4DIP):c.879C>T(p.Ser293Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,442,728 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

PDE4DIP
NM_001395297.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

Publications

0 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=-0.51).

BP6

Variant 1-148953659-C-T is Benign according to our data. Variant chr1-148953659-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639077.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395297.1. 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.835-6995C>T		intron	N/A	NP_001382355.1	A0A8Q3SI83
PDE4DIP	NM_001395297.1		c.879C>T	p.Ser293Ser	synonymous	Exon 1 of 40	NP_001382226.1
PDE4DIP	NM_001350520.2		c.879C>T	p.Ser293Ser	synonymous	Exon 1 of 40	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDE4DIP	ENST00000313431.13	TSL:1	c.879C>T	p.Ser293Ser	synonymous	Exon 1 of 19	ENSP00000316434.9	Q5VU43-2
PDE4DIP	ENST00000529945.2	TSL:1	c.879C>T	p.Ser293Ser	synonymous	Exon 1 of 17	ENSP00000433392.1	Q5VU43-13
PDE4DIP	ENST00000695795.1	MANE Select	c.835-6995C>T		intron	N/A	ENSP00000512175.1	A0A8Q3SI83

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000215

AC:

AN:

251478

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000102

AC:

131

AN:

1290522

Hom.:

Cov.:

AF XY:

0.0000938

AC XY:

AN XY:

650638

show subpopulations

African (AFR)

AF:

0.00301

AC:

AN:

30268

American (AMR)

AF:

0.000485

AC:

AN:

43342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24854

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38958

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52774

Middle Eastern (MID)

AF:

0.000367

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

0.00000209

AC:

AN:

958142

Other (OTH)

AF:

0.000220

AC:

AN:

54492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00108

AC:

164

AN:

152206

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00373

AC:

155

AN:

41532

American (AMR)

AF:

0.000393

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.000238

Hom.:

Bravo

AF:

0.00106

ClinVar

ClinVar submissions as Germline

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

-0.51

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.4

Mutation Taster

=92/8

polymorphism

(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