1-148962551-C-T

Position:

• chr1-148962551-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP3_Moderate BP6_Very_Strong BP7

The NM_001395426.1(PDE4DIP):​c.1303C>T​(p.Leu435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PDE4DIP NM_001395426.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58

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 Benign. Variant got -7 ACMG points.

• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.33
• BP6: Variant 1-148962551-C-T is Benign according to our data. Variant chr1-148962551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 769527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4DIP	NM_001395426.1	c.1303C>T	p.Leu435=	synonymous_variant	12/47	ENST00000695795.1	NP_001382355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4DIP	ENST00000695795.1	c.1303C>T	p.Leu435=	synonymous_variant	12/47		NM_001395426.1	ENSP00000512175

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD3 exomes AF: 0.187 AC: 45152 AN: 240946 Hom.: 0 AF XY: 0.185 AC XY: 24141 AN XY: 130204

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.391

Gnomad SAS exome AF: 0.178

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.00000196 AC: 1 AN: 510188 Hom.: 0 Cov.: 5 AF XY: 0.00000368 AC XY: 1 AN XY: 272004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000332

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 16

Alfa AF: 0.110 Hom.: 134

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 04, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.33
CADD	Benign	14
DANN	Benign	0.85

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: rs71664015; hg19: chr1-144921924; COSMIC: COSV57684451; COSMIC: COSV57684451;