ENST00000313431.13:c.622A>G

Variant names:

• chr1-148953402-A-G
• rs41315684
• ENST00000313431.13:c.622A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM2 BP4_Moderate BP6_Very_Strong

The ENST00000313431.13(PDE4DIP):​c.622A>G​(p.Thr208Ala) variant causes a missense 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. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDE4DIP ENST00000313431.13 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.52
• Publications: 15 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14725709).
• BP6: Variant 1-148953402-A-G is Benign according to our data. Variant chr1-148953402-A-G is described in ClinVar as Benign. ClinVar VariationId is 767695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.835-7252A>G		intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.622A>G	p.Thr208Ala	missense	Exon 1 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.622A>G	p.Thr208Ala	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.622A>G	p.Thr208Ala	missense	Exon 1 of 19	ENSP00000316434.9	Q5VU43-2
	PDE4DIP	ENST00000529945.2	TSL:1	c.622A>G	p.Thr208Ala	missense	Exon 1 of 17	ENSP00000433392.1	Q5VU43-13
	PDE4DIP	ENST00000695795.1	MANE Select	c.835-7252A>G		intron	N/A	ENSP00000512175.1	A0A8Q3SI83

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.218 AC: 48960 AN: 224256 AF XY: 0.228

Gnomad AFR exome AF: 0.0494

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.224

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.273 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	Benign	0.096
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.97
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.15	T
PhyloP100		2.5
PROVEAN	Benign	-1.3	N
Sift	Benign	0.43	T
Sift4G	Benign	0.31	T
Vest4		0.23

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: rs41315684; hg19: chr1-144931087; COSMIC: COSV57697851;