1-148962237-A-G

Variant names:

• chr1-148962237-A-G
• NM_001395426.1:c.1128A>G
• PDE4DIP p.Thr376Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001395426.1(PDE4DIP):​c.1128A>G​(p.Thr376Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T376T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-3.07 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.1128A>G	p.Thr376Thr	synonymous	Exon 11 of 47	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.1419A>G	p.Thr473Thr	synonymous	Exon 4 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.1419A>G	p.Thr473Thr	synonymous	Exon 4 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.1128A>G	p.Thr376Thr	synonymous	Exon 11 of 47	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.930A>G	p.Thr310Thr	synonymous	Exon 8 of 44	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.930A>G	p.Thr310Thr	synonymous	Exon 8 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1003222 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 515162

African (AFR) AF: 0.00 AC: 0 AN: 24808

American (AMR) AF: 0.00 AC: 0 AN: 40032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22788

East Asian (EAS) AF: 0.00 AC: 0 AN: 36790

South Asian (SAS) AF: 0.00 AC: 0 AN: 73658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4936

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 709780

Other (OTH) AF: 0.00 AC: 0 AN: 45338

GnomAD4 genome Cov.: 23

EpiCase AF: 0.00186

EpiControl AF: 0.00107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.60
PhyloP100		-3.1
Mutation Taster		=62/38	polymorphism

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

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

Other links and lift over

hg19: chr1-144922238;