Variant chr6-136154165-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_018945.4(PDE7B):c.569A>C(p.Lys190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,458,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 2.50

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4201513).

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.569A>C	p.Lys190Thr	missense_variant	7/13	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.569A>C	p.Lys190Thr	missense_variant	7/13	1	NM_018945.4	ENSP00000310661	P1
PDE7B-AS1	ENST00000655618.1 linkuse as main transcript	n.178+8087T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250412

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

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:

0.0000265

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1458864

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

725926

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000995

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

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

Jan 10, 2023

The c.569A>C (p.K190T) alteration is located in exon 7 (coding exon 7) of the PDE7B gene. This alteration results from a A to C substitution at nucleotide position 569, causing the lysine (K) at amino acid position 190 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.038

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.35

Sift

Benign

0.056

T;.

Sift4G

Benign

0.28

T;T

Polyphen

0.16

B;P

Vest4

0.60

MVP

0.46

MPC

0.76

ClinPred

0.21

GERP RS

1.9

Varity_R

0.18

gMVP

0.40

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.

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