Variant rs3821010 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016953.4(PDE11A):c.1577-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,396,904 control chromosomes in the GnomAD database, including 75,446 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14371 hom., cov: 31)

Exomes 𝑓: 0.31 ( 61075 hom. )

Consequence

PDE11A
NM_016953.4 splice_region, intron

Scores

Splicing: ADA: 0.00004978

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

PDE11A (HGNC:8773): (phosphodiesterase 11A) 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 member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PDE11A links:

PDE11A (HGNC:):

PDE11A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 2-177817928-A-G is Benign according to our data. Variant chr2-177817928-A-G is described in ClinVar as [Benign]. Clinvar id is 1327001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-177817928-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PDE11A	NM_016953.4 linkuse as main transcript	c.1577-3T>C	splice_region_variant, intron_variant	ENST00000286063.11	NP_058649.3	Q9HCR9-1
PDE11A	NM_001077197.2 linkuse as main transcript	c.827-3T>C	splice_region_variant, intron_variant		NP_001070665.1	Q9HCR9-2
PDE11A	NM_001077358.2 linkuse as main transcript	c.503-3T>C	splice_region_variant, intron_variant		NP_001070826.1	Q9HCR9-3
PDE11A	NM_001077196.2 linkuse as main transcript	c.245-3T>C	splice_region_variant, intron_variant		NP_001070664.1	Q9HCR9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11 linkuse as main transcript	c.1577-3T>C		splice_region_variant, intron_variant		1	NM_016953.4	ENSP00000286063.5		Q9HCR9-1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61646

AN:

151786

Hom.:

14355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.324

AC:

81066

AN:

250122

Hom.:

14669

AF XY:

0.325

AC XY:

43891

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.648

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.314

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.305

AC:

380217

AN:

1245000

Hom.:

61075

Cov.:

AF XY:

0.308

AC XY:

194133

AN XY:

630134

show subpopulations

Gnomad4 AFR exome

AF:

0.640

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.298

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.297

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.406

AC:

61704

AN:

151904

Hom.:

14371

Cov.:

AF XY:

0.400

AC XY:

29705

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.349

Hom.:

15889

Bravo

AF:

0.422

Asia WGS

AF:

0.297

AC:

1035

AN:

3478

EpiCase

AF:

0.339

EpiControl

AF:

0.347

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Pigmented nodular adrenocortical disease, primary, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.7

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.0020

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