chr6-136191773-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018945.4(PDE7B):​c.1286G>A​(p.Ser429Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,432,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

PDE7B
NM_018945.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.160
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-AS1 (HGNC:56334): (PDE7B antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05527371).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDE7BNM_018945.4 linkuse as main transcriptc.1286G>A p.Ser429Asn missense_variant 13/13 ENST00000308191.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDE7BENST00000308191.11 linkuse as main transcriptc.1286G>A p.Ser429Asn missense_variant 13/131 NM_018945.4 P1
PDE7B-AS1ENST00000655618.1 linkuse as main transcriptn.82-29425C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000154
AC:
3
AN:
195298
Hom.:
0
AF XY:
0.0000189
AC XY:
2
AN XY:
105636
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000358
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000698
AC:
10
AN:
1432992
Hom.:
0
Cov.:
31
AF XY:
0.00000704
AC XY:
5
AN XY:
710704
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000911
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0
ExAC
AF:
0.00000832
AC:
1

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 submitterclinical testingAmbry GeneticsNov 17, 2022The c.1286G>A (p.S429N) alteration is located in exon 13 (coding exon 13) of the PDE7B gene. This alteration results from a G to A substitution at nucleotide position 1286, causing the serine (S) at amino acid position 429 to be replaced by an asparagine (N). 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
0.074
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
14
DANN
Benign
0.95
DEOGEN2
Benign
0.070
T;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.055
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.57
N;.
REVEL
Benign
0.094
Sift
Benign
0.25
T;.
Sift4G
Benign
0.49
T;T
Polyphen
0.0
B;B
Vest4
0.030
MutPred
0.21
Loss of glycosylation at S429 (P = 0.0038);.;
MVP
0.16
MPC
0.30
ClinPred
0.046
T
GERP RS
3.8
Varity_R
0.080
gMVP
0.22

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

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

Other links and lift over

dbSNP: rs766588065; hg19: chr6-136512911; API