1-148962237-A-C

Variant names:

• chr1-148962237-A-C
• rs144426043
• NM_001395426.1:c.1128A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001395426.1(PDE4DIP):​c.1128A>C​(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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: PDE4DIP NM_001395426.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.07
• Publications: 2 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 1-148962237-A-C is Benign according to our data. Variant chr1-148962237-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2639076.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>C	p.Thr376Thr	synonymous	Exon 11 of 47	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.1419A>C	p.Thr473Thr	synonymous	Exon 4 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.1419A>C	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>C	p.Thr376Thr	synonymous	Exon 11 of 47	ENSP00000512175.1	A0A8Q3SI83
	PDE4DIP	ENST00000369356.8	TSL:1	c.930A>C	p.Thr310Thr	synonymous	Exon 8 of 44	ENSP00000358363.4	Q5VU43-4
	PDE4DIP	ENST00000369354.7	TSL:1	c.930A>C	p.Thr310Thr	synonymous	Exon 8 of 44	ENSP00000358360.3	Q5VU43-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.000860 AC: 216 AN: 251206 AF XY: 0.000832

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.00147

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 23

Alfa AF: 0.00213 Hom.: 0

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	-0.62
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		-3.1
Mutation Taster		=58/42	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

Other links and lift over

dbSNP: rs144426043; hg19: chr1-144922238;