rs147815016

Variant names:

• chr1-149003009-G-A
• rs147815016
• NM_001395426.1:c.3931G>A
• PDE4DIP p.Ala1311Thr

Your query was ambiguous. Multiple possible variants found:

• chr1-149003009-G-A
• chr1-149003009-G-C
• chr1-149003009-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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 VariationId is 3024762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

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.3931G>A	p.Ala1311Thr	missense	Exon 28 of 47	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.4222G>A	p.Ala1408Thr	missense	Exon 21 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.4222G>A	p.Ala1408Thr	missense	Exon 21 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.3931G>A	p.Ala1311Thr	missense	Exon 28 of 47	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.3733G>A	p.Ala1245Thr	missense	Exon 25 of 44	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.3733G>A	p.Ala1245Thr	missense	Exon 25 of 44	ENSP00000358360.3	Q5VU43-1

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

GnomAD2 exomes AF: 0.00342 AC: 858 AN: 250922 AF XY: 0.00354

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 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

African (AFR) AF: 0.00148 AC: 22 AN: 14906

American (AMR) AF: 0.00763 AC: 213 AN: 27914

Ashkenazi Jewish (ASJ) AF: 0.00320 AC: 47 AN: 14696

East Asian (EAS) AF: 0.00 AC: 0 AN: 35418

South Asian (SAS) AF: 0.000376 AC: 20 AN: 53136

European-Finnish (FIN) AF: 0.000528 AC: 26 AN: 49282

Middle Eastern (MID) AF: 0.00508 AC: 11 AN: 2164

European-Non Finnish (NFE) AF: 0.00664 AC: 2228 AN: 335592

Other (OTH) AF: 0.00611 AC: 182 AN: 29770

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

African (AFR) AF: 0.00179 AC: 73 AN: 40778

American (AMR) AF: 0.00869 AC: 131 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.00204 AC: 7 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4676

European-Finnish (FIN) AF: 0.000480 AC: 5 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00682 AC: 459 AN: 67312

Other (OTH) AF: 0.0111 AC: 23 AN: 2080

Alfa AF: 0.00582 Hom.: 0

Bravo AF: 0.00569

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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
AlphaMissense	Benign	0.16
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.088	T
PhyloP100		5.5
PROVEAN	Benign	-2.1	N
Sift	Benign	0.064	T
Sift4G	Benign	0.13	T
gMVP		0.58

Splicing

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