Variant 6-136181230-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_018945.4(PDE7B):c.952G>T(p.Ala318Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,458,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PDE7B
NM_018945.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.11

Variant links:

Genes affected

PDE7B (HGNC:8792): (phosphodiesterase 7B) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a cAMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family.[provided by RefSeq, Apr 2009]

PDE7B links:

PDE7B-AS1 (HGNC:56334): (PDE7B antisense RNA 1)

PDE7B-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE7B	NM_018945.4 linkuse as main transcript	c.952G>T	p.Ala318Ser	missense_variant	11/13	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11 linkuse as main transcript	c.952G>T	p.Ala318Ser	missense_variant	11/13	1	NM_018945.4	ENSP00000310661	P1
PDE7B-AS1	ENST00000655618.1 linkuse as main transcript	n.82-18882C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1458992

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 05, 2023

The c.952G>T (p.A318S) alteration is located in exon 11 (coding exon 11) of the PDE7B gene. This alteration results from a G to T substitution at nucleotide position 952, causing the alanine (A) at amino acid position 318 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

Benign

0.21

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Uncertain

0.089

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.4

N;.

REVEL

Uncertain

0.61

Sift

Benign

0.092

T;.

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.56

Loss of ubiquitination at K320 (P = 0.0736);.;

MVP

0.66

MPC

1.0

ClinPred

0.99

GERP RS

4.9

Varity_R

0.55

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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