6-136154165-A-C

Variant names:

• chr6-136154165-A-C
• rs776406458
• NM_018945.4:c.569A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4201513).
• BS2: High AC in GnomAdExome4 at 33 AD gene.

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.569A>C	p.Lys190Thr	missense	Exon 7 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.569A>C	p.Lys190Thr	missense	Exon 7 of 13	ENSP00000310661.6	Q9NP56
	PDE7B	ENST00000615259.4	TSL:1	c.725A>C	p.Lys242Thr	missense	Exon 6 of 12	ENSP00000482117.1	A1E5M1
	PDE7B	ENST00000446774.1	TSL:5	c.251A>C	p.Lys84Thr	missense	Exon 3 of 4	ENSP00000403732.1	H0Y689

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250412 AF XY: 0.0000369

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1458864 Hom.: 0 Cov.: 29 AF XY: 0.0000193 AC XY: 14 AN XY: 725926

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.0000671 AC: 3 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1109436

Other (OTH) AF: 0.0000995 AC: 6 AN: 60302

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000762 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000330 AC: 4

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	Benign	0.16
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.038
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.35
Sift	Benign	0.056	T
Sift4G	Benign	0.28	T
Polyphen		0.16	B
Vest4		0.60
MVP		0.46
MPC		0.76
ClinPred		0.21	T
GERP RS		1.9
Varity_R		0.18
gMVP		0.40
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

dbSNP: rs776406458; hg19: chr6-136475303;