NM_002600.4:c.449C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002600.4(PDE4B):​c.449C>G​(p.Ser150Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,593,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S150L) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

PDE4B
NM_002600.4 missense

Scores

13
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.71
Variant links:
Genes affected
PDE4B (HGNC:8781): (phosphodiesterase 4B) This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. The encoded protein regulates the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDE4BNM_002600.4 linkc.449C>G p.Ser150Trp missense_variant Exon 4 of 17 ENST00000341517.9 NP_002591.2 Q07343-1X5DNX5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDE4BENST00000341517.9 linkc.449C>G p.Ser150Trp missense_variant Exon 4 of 17 1 NM_002600.4 ENSP00000342637.4 Q07343-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000857
AC:
2
AN:
233460
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
126494
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:
0.0000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1441590
Hom.:
0
Cov.:
31
AF XY:
0.00000140
AC XY:
1
AN XY:
716656
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:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.87
D;D;.;D
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
1.0
.;D;D;D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.83
D;D;D;D
MetaSVM
Uncertain
0.58
D
MutationAssessor
Pathogenic
3.1
M;M;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-5.6
D;D;D;D
REVEL
Uncertain
0.64
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.84
MutPred
0.32
Loss of disorder (P = 0.0084);Loss of disorder (P = 0.0084);.;.;
MVP
0.86
MPC
1.6
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs370994595; hg19: chr1-66713310; API