6-136155659-G-A

Variant names:

• chr6-136155659-G-A
• NM_018945.4:c.612G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018945.4(PDE7B):​c.612G>A​(p.Met204Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PDE7B NM_018945.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3292462).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018945.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	NM_018945.4	MANE Select	c.612G>A	p.Met204Ile	missense	Exon 8 of 13	NP_061818.1	Q9NP56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	ENST00000308191.11	TSL:1 MANE Select	c.612G>A	p.Met204Ile	missense	Exon 8 of 13	ENSP00000310661.6	Q9NP56
	PDE7B	ENST00000615259.4	TSL:1	c.768G>A	p.Met256Ile	missense	Exon 7 of 12	ENSP00000482117.1	A1E5M1
	PDE7B	ENST00000446774.1	TSL:5	c.294G>A	p.Met98Ile	missense	Exon 4 of 4	ENSP00000403732.1	H0Y689

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.43
Sift	Benign	0.038	D
Sift4G	Uncertain	0.042	D
Polyphen		0.061	B
Vest4		0.54
MutPred		0.60		Loss of helix (P = 0.2271)
MVP		0.36
MPC		0.43
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.56
gMVP		0.56
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

hg19: chr6-136476797;