1-148953659-C-G

Variant names:

• chr1-148953659-C-G
• rs140994384
• ENST00000313431.13:c.879C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395297.1(PDE4DIP):​c.879C>G​(p.Ser293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000775 in 1,290,524 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S293S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: PDE4DIP NM_001395297.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19284856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395297.1. 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.835-6995C>G		intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.879C>G	p.Ser293Arg	missense	Exon 1 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.879C>G	p.Ser293Arg	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.879C>G	p.Ser293Arg	missense	Exon 1 of 19	ENSP00000316434.9	Q5VU43-2
	PDE4DIP	ENST00000529945.2	TSL:1	c.879C>G	p.Ser293Arg	missense	Exon 1 of 17	ENSP00000433392.1	Q5VU43-13
	PDE4DIP	ENST00000695795.1	MANE Select	c.835-6995C>G		intron	N/A	ENSP00000512175.1	A0A8Q3SI83

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251478 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.75e-7 AC: 1 AN: 1290524 Hom.: 0 Cov.: 19 AF XY: 0.00000154 AC XY: 1 AN XY: 650640

African (AFR) AF: 0.00 AC: 0 AN: 30270

American (AMR) AF: 0.00 AC: 0 AN: 43342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24854

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38958

South Asian (SAS) AF: 0.00 AC: 0 AN: 82244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 958142

Other (OTH) AF: 0.00 AC: 0 AN: 54492

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.19	T
PhyloP100		1.4
PROVEAN	Benign	-1.3	N
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Vest4		0.21

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: rs140994384; hg19: chr1-144930830;