rs146047382

Variant names:

• chr1-148962565-A-G
• rs146047382
• NM_001395426.1:c.1317A>G
• PDE4DIP p.Lys439Lys

Your query was ambiguous. Multiple possible variants found:

• chr1-148962565-A-G
• chr1-148962565-A-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106
• Publications: 3 publications found

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

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

Sel.	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

Sel.	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.: 0 Cov.: 16

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: 64 AN: 251478 AF XY: 0.000140

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: 75 AN: 501478 Hom.: 0 Cov.: 5 AF XY: 0.000127 AC XY: 34 AN XY: 267082

African (AFR) AF: 0.00326 AC: 47 AN: 14402

American (AMR) AF: 0.000595 AC: 15 AN: 25214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15530

East Asian (EAS) AF: 0.00 AC: 0 AN: 33520

South Asian (SAS) AF: 0.00 AC: 0 AN: 52240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33476

Middle Eastern (MID) AF: 0.000405 AC: 1 AN: 2472

European-Non Finnish (NFE) AF: 0.00000675 AC: 2 AN: 296432

Other (OTH) AF: 0.000355 AC: 10 AN: 28192

GnomAD4 genome AF: 0.00116 AC: 148 AN: 127452 Hom.: 0 Cov.: 16 AF XY: 0.00109 AC XY: 66 AN XY: 60568

African (AFR) AF: 0.00428 AC: 139 AN: 32486

American (AMR) AF: 0.000496 AC: 6 AN: 12086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3154

East Asian (EAS) AF: 0.00 AC: 0 AN: 4480

South Asian (SAS) AF: 0.00 AC: 0 AN: 3230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000327 AC: 2 AN: 61120

Other (OTH) AF: 0.000622 AC: 1 AN: 1608

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.00128

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.58
PhyloP100		0.11
Mutation Taster		=91/9	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs146047382; hg19: chr1-144921910;