1-149003009-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001395426.1(PDE4DIP):c.3931G>A(p.Ala1311Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 20)
  • Exomes 𝑓: 0.0049 (12 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.46

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08840865).
• BP6: Variant 1-149003009-G-A is Benign according to our data. Variant chr1-149003009-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4DIP	NM_001395426.1	c.3931G>A	p.Ala1311Thr	missense_variant	28/47	ENST00000695795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4DIP	ENST00000695795.1	c.3931G>A	p.Ala1311Thr	missense_variant	28/47		NM_001395426.1

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 701 AN: 149942 Hom.: 4 Cov.: 20

Gnomad AFR AF: 0.00180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.00204

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.000480

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00682

Gnomad OTH AF: 0.0112

GnomAD3 exomes AF: 0.00342 AC: 858 AN: 250922 Hom.: 0 AF XY: 0.00354 AC XY: 480 AN XY: 135578

Gnomad AFR exome AF: 0.000924

Gnomad AMR exome AF: 0.00533

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00526

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00488 AC: 2749 AN: 562878 Hom.: 12 Cov.: 6 AF XY: 0.00479 AC XY: 1439 AN XY: 300482

Gnomad4 AFR exome AF: 0.00148

Gnomad4 AMR exome AF: 0.00763

Gnomad4 ASJ exome AF: 0.00320

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000376

Gnomad4 FIN exome AF: 0.000528

Gnomad4 NFE exome AF: 0.00664

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00466 AC: 699 AN: 150054 Hom.: 3 Cov.: 20 AF XY: 0.00395 AC XY: 289 AN XY: 73144

Gnomad4 AFR AF: 0.00179

Gnomad4 AMR AF: 0.00869

Gnomad4 ASJ AF: 0.00204

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.000480

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.0111

Alfa AF: 0.00610 Hom.: 0

Bravo AF: 0.00569

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

PDE4DIP: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_noAF	Pathogenic	0.33
Cadd	Pathogenic	26
Dann	Uncertain	1.0
LIST_S2	Uncertain	0.91	D;D;T;D;D
MetaRNN	Benign	0.088	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Vest4		0.59
gMVP		0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147815016; hg19: chr1-144881463; COSMIC: COSV100521212; COSMIC: COSV100521212;