Variant chr1-149002952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBP4

The NM_001395426.1(PDE4DIP):c.3874C>T(p.Arg1292Cys) variant causes a missense 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 pathogenic (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00020 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PDE4DIP
NM_001395426.1 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.57

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 1-149002952-C-T is Pathogenic according to our data. Variant chr1-149002952-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1174535.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.17757362). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4DIP	NM_001395426.1 linkuse as main transcript	c.3874C>T	p.Arg1292Cys	missense_variant	28/47	ENST00000695795.1	NP_001382355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4DIP	ENST00000695795.1 linkuse as main transcript	c.3874C>T	p.Arg1292Cys	missense_variant	28/47		NM_001395426.1	ENSP00000512175

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

140930

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000772

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251360

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000197

AC:

113

AN:

574840

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

306368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000272

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.0000707

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000170

AC:

AN:

141024

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

AN XY:

67958

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00199

Gnomad4 NFE

AF:

0.0000772

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Mani Lab, Yale Cardiovascular Research Center, Yale University

Jun 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.074

.;T;.;.;T

LIST_S2

Uncertain

0.87

D;D;D;D;D

MetaRNN

Benign

0.18

T;T;T;T;T

PROVEAN

Uncertain

-3.4

.;.;.;D;D

Sift

Uncertain

0.0010

.;.;.;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Vest4

0.36

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over