ENST00000313431.13:c.322A>C

Variant names:

• chr1-148953102-A-C
• rs61805374
• ENST00000313431.13:c.322A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000313431.13(PDE4DIP):​c.322A>C​(p.Ile108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,613,942 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0049 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0080 (49 hom.)
• Consequence: PDE4DIP ENST00000313431.13 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.857
• Publications: 12 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=0.0148049295).
• BS2: High Homozygotes in GnomAdExome4 at 49 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313431.13. 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.835-7552A>C		intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.322A>C	p.Ile108Leu	missense	Exon 1 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.322A>C	p.Ile108Leu	missense	Exon 1 of 40	NP_001337449.1	A0A994J5E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4DIP	ENST00000313431.13	TSL:1	c.322A>C	p.Ile108Leu	missense	Exon 1 of 19	ENSP00000316434.9	Q5VU43-2
	PDE4DIP	ENST00000529945.2	TSL:1	c.322A>C	p.Ile108Leu	missense	Exon 1 of 17	ENSP00000433392.1	Q5VU43-13
	PDE4DIP	ENST00000695795.1	MANE Select	c.835-7552A>C		intron	N/A	ENSP00000512175.1	A0A8Q3SI83

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 743 AN: 152076 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00813

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00473 AC: 1189 AN: 251144 AF XY: 0.00463

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00504

Gnomad NFE exome AF: 0.00809

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00798 AC: 11660 AN: 1461748 Hom.: 49 Cov.: 32 AF XY: 0.00774 AC XY: 5626 AN XY: 727162

African (AFR) AF: 0.000777 AC: 26 AN: 33478

American (AMR) AF: 0.00300 AC: 134 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 77 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86254

European-Finnish (FIN) AF: 0.00589 AC: 314 AN: 53324

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00960 AC: 10674 AN: 1111992

Other (OTH) AF: 0.00705 AC: 426 AN: 60386

GnomAD4 genome AF: 0.00488 AC: 743 AN: 152194 Hom.: 0 Cov.: 31 AF XY: 0.00405 AC XY: 301 AN XY: 74404

African (AFR) AF: 0.00176 AC: 73 AN: 41516

American (AMR) AF: 0.00301 AC: 46 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00481 AC: 51 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00813 AC: 553 AN: 68016

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00697 Hom.: 1

Bravo AF: 0.00493

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.75
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.015	T
PhyloP100		0.86
PROVEAN	Benign	-0.15	N
Sift	Benign	0.29	T
Sift4G	Benign	0.26	T
Vest4		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs61805374; hg19: chr1-144931387; COSMIC: COSV57675492;