6-136149088-A-T

Variant names:

• chr6-136149088-A-T
• rs754900327
• NM_018945.4:c.320A>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_018945.4(PDE7B):​c.320A>T​(p.His107Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000411 in 1,458,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. H107R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PDE7B NM_018945.4 missense, splice_region
• Scores: Splicing: ADA: 0.8337
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29074946).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.320A>T	p.His107Leu	missense_variant, splice_region_variant	Exon 5 of 13	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.320A>T	p.His107Leu	missense_variant, splice_region_variant	Exon 5 of 13	1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251162 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135736

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: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458414 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 725780

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: 0.00000541

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.5	N;.
REVEL	Uncertain	0.44
Sift	Benign	0.16	T;.
Sift4G	Benign	0.18	T;T
Polyphen		0.90	P;D
Vest4		0.54
MutPred		0.34		Loss of methylation at K111 (P = 0.0722);.;
MVP		0.39
MPC		0.85
ClinPred		0.55	D
GERP RS		5.4
Varity_R		0.29
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.83
dbscSNV1_RF	Pathogenic	0.74
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

Other links and lift over

dbSNP: rs754900327; hg19: chr6-136470226;