Variant 8-65779747-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001242318.3(PDE7A):c.256C>T(p.Pro86Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,439,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PDE7A
NM_001242318.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15

Variant links:

Genes affected

PDE7A (HGNC:8791): (phosphodiesterase 7A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE7 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

PDE7A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PDE7A	NM_001242318.3 linkuse as main transcript	c.256C>T	p.Pro86Ser	missense_variant	3/13	ENST00000401827.8	NP_001229247.1
PDE7A	NM_002603.4 linkuse as main transcript	c.178C>T	p.Pro60Ser	missense_variant	3/13		NP_002594.1
PDE7A	XM_011517540.4 linkuse as main transcript	c.178C>T	p.Pro60Ser	missense_variant	4/14		XP_011515842.1
PDE7A	XM_017013538.3 linkuse as main transcript	c.154C>T	p.Pro52Ser	missense_variant	3/13		XP_016869027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE7A	ENST00000401827.8 linkuse as main transcript	c.256C>T	p.Pro86Ser	missense_variant	3/13	1	NM_001242318.3	ENSP00000385632	P4	Q13946-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000826

AC:

AN:

242088

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1439620

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000104

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.256C>T (p.P86S) alteration is located in exon 1 (coding exon 1) of the PDE7A gene. This alteration results from a C to T substitution at nucleotide position 256, causing the proline (P) at amino acid position 86 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;.;.;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.0

M;.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Benign

0.071

T;D;T;.

Polyphen

0.98

D;P;D;.

Vest4

0.71

MutPred

0.29

Gain of phosphorylation at P86 (P = 0.0388);.;Gain of phosphorylation at P86 (P = 0.0388);.;

MVP

0.83

MPC

0.82

ClinPred

0.80

GERP RS

5.9

Varity_R

0.24

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over