1-148931908-C-G

Position:

• chr1-148931908-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395426.1(PDE4DIP):​c.525C>G​(p.Ile175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 151,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 24)
  • Exomes 𝑓: 0.00025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.07

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034126908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4DIP	NM_001395426.1	c.525C>G	p.Ile175Met	missense_variant	6/47	ENST00000695795.1	NP_001382355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4DIP	ENST00000695795.1	c.525C>G	p.Ile175Met	missense_variant	6/47		NM_001395426.1	ENSP00000512175

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 641 AN: 150964 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000843

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000398

Gnomad OTH AF: 0.00241

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000245 AC: 352 AN: 1434098 Hom.: 0 Cov.: 27 AF XY: 0.000252 AC XY: 180 AN XY: 714954

Gnomad4 AFR exome AF: 0.00463

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000599

Gnomad4 FIN exome AF: 0.000676

Gnomad4 NFE exome AF: 0.0000671

Gnomad4 OTH exome AF: 0.000421

GnomAD4 genome AF: 0.00426 AC: 644 AN: 151078 Hom.: 1 Cov.: 24 AF XY: 0.00421 AC XY: 311 AN XY: 73854

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.00139

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000844

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.000398

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.155 Hom.: 9

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hepatocellular carcinoma Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.85
DEOGEN2	Benign	0.076	.;.;T;.;.;.;.;T;.;.;.
LIST_S2	Benign	0.73	T;T;T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.034	T;T;T;T;T;T;T;T;T;T;T
PROVEAN	Uncertain	-2.4	.;.;.;.;.;N;N;N;N;N;N
Sift	Benign	0.050	.;.;.;.;.;D;D;D;T;D;D
Sift4G	Uncertain	0.024	D;T;T;D;D;D;T;T;D;T;T
Vest4		0.46
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs605611; hg19: chr1-144952581; COSMIC: COSV57673102; COSMIC: COSV57673102;