ENST00000313431.13:c.732T>G

Variant names:

• chr1-148953512-T-G
• rs143410813
• ENST00000313431.13:c.732T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000313431.13(PDE4DIP):​c.732T>G​(p.Ser244Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,613,870 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0037 (9 hom.)
• Consequence: PDE4DIP ENST00000313431.13 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 1-148953512-T-G is Benign according to our data. Variant chr1-148953512-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2639078.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.103 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.835-7142T>G		intron	N/A	NP_001382355.1	A0A8Q3SI83
	PDE4DIP	NM_001395297.1		c.732T>G	p.Ser244Ser	synonymous	Exon 1 of 40	NP_001382226.1
	PDE4DIP	NM_001350520.2		c.732T>G	p.Ser244Ser	synonymous	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.732T>G	p.Ser244Ser	synonymous	Exon 1 of 19	ENSP00000316434.9	Q5VU43-2
	PDE4DIP	ENST00000529945.2	TSL:1	c.732T>G	p.Ser244Ser	synonymous	Exon 1 of 17	ENSP00000433392.1	Q5VU43-13
	PDE4DIP	ENST00000695795.1	MANE Select	c.835-7142T>G		intron	N/A	ENSP00000512175.1	A0A8Q3SI83

Frequencies

GnomAD3 genomes AF: 0.00300 AC: 456 AN: 152210 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00395

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00379 AC: 952 AN: 251186 AF XY: 0.00436

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.0150

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00431

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00373 AC: 5451 AN: 1461542 Hom.: 9 Cov.: 32 AF XY: 0.00400 AC XY: 2909 AN XY: 727098

African (AFR) AF: 0.000359 AC: 12 AN: 33466

American (AMR) AF: 0.00282 AC: 126 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 430 AN: 26124

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00729 AC: 629 AN: 86232

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53420

Middle Eastern (MID) AF: 0.0133 AC: 77 AN: 5768

European-Non Finnish (NFE) AF: 0.00348 AC: 3870 AN: 1111802

Other (OTH) AF: 0.00477 AC: 288 AN: 60370

GnomAD4 genome AF: 0.00299 AC: 456 AN: 152328 Hom.: 0 Cov.: 31 AF XY: 0.00290 AC XY: 216 AN XY: 74488

African (AFR) AF: 0.000361 AC: 15 AN: 41590

American (AMR) AF: 0.00405 AC: 62 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4832

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00395 AC: 269 AN: 68018

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00345 Hom.: 0

Bravo AF: 0.00321

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.57
PhyloP100		0.10
Mutation Taster		=75/25	polymorphism

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: rs143410813; hg19: chr1-144930977;