rs41315685

Variant names:

• chr1-148953028-T-A
• rs41315685
• ENST00000313431.13:c.248T>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 3P and 8B. PM2 PP3 BP6_Very_Strong

The NM_001395297.1(PDE4DIP):​c.248T>A​(p.Leu83Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE4DIP NM_001395297.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.86
• Publications: 20 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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808
• BP6: Variant 1-148953028-T-A is Benign according to our data. Variant chr1-148953028-T-A is described in ClinVar as Benign. ClinVar VariationId is 767696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.835-7626T>A		intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.248T>A	p.Leu83Gln	missense	Exon 1 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.248T>A	p.Leu83Gln	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.248T>A	p.Leu83Gln	missense	Exon 1 of 19	ENSP00000316434.9	Q5VU43-2
	PDE4DIP	ENST00000529945.2	TSL:1	c.248T>A	p.Leu83Gln	missense	Exon 1 of 17	ENSP00000433392.1	Q5VU43-13
	PDE4DIP	ENST00000695795.1	MANE Select	c.835-7626T>A		intron	N/A	ENSP00000512175.1	A0A8Q3SI83

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.239 AC: 53130 AN: 222650 AF XY: 0.247

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.241

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.289 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
LIST_S2	Uncertain	0.89	D
MetaRNN	Pathogenic	0.81	D
PhyloP100		7.9
PROVEAN	Benign	-2.3	N
Sift	Benign	0.071	T
Sift4G	Uncertain	0.0020	D
Vest4		0.80

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: rs41315685; hg19: chr1-144931461; COSMIC: COSV57695188;