rs11676272

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004036.5(ADCY3):c.319T>C(p.Ser107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,613,848 control chromosomes in the GnomAD database, including 200,579 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 26559 hom., cov: 32)

Exomes 𝑓: 0.48 ( 174020 hom. )

Consequence

ADCY3
NM_004036.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.33

Publications

116 publications found

Variant links:

Genes affected

ADCY3 (HGNC:234): (adenylate cyclase 3) This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ADCY3 Gene-Disease associations (from GenCC):

body mass index quantitative trait locus 19
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ADCY3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.1551988E-6).

BP6

Variant 2-24918669-A-G is Benign according to our data. Variant chr2-24918669-A-G is described in ClinVar as Benign. ClinVar VariationId is 1541304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004036.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY3	NM_004036.5	MANE Select	c.319T>C	p.Ser107Pro	missense	Exon 2 of 22	NP_004027.2	O60266-1
ADCY3	NM_001377128.1		c.319T>C	p.Ser107Pro	missense	Exon 2 of 23	NP_001364057.1
ADCY3	NM_001320613.2		c.319T>C	p.Ser107Pro	missense	Exon 2 of 22	NP_001307542.1	A0A0A0MSC1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY3	ENST00000679454.1	MANE Select	c.319T>C	p.Ser107Pro	missense	Exon 2 of 22	ENSP00000505261.1	O60266-1
ADCY3	ENST00000405392.6	TSL:1	c.319T>C	p.Ser107Pro	missense	Exon 1 of 21	ENSP00000384484.2	A0A0A0MSC1
ADCY3	ENST00000260600.9	TSL:1	c.319T>C	p.Ser107Pro	missense	Exon 1 of 21	ENSP00000260600.5	O60266-1

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85224

AN:

151980

Hom.:

26498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.529

GnomAD2 exomes

AF:

0.466

AC:

117121

AN:

251328

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.856

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.470

Gnomad OTH exome

AF:

0.452

GnomAD4 exome

AF:

0.482

AC:

704605

AN:

1461750

Hom.:

174020

Cov.:

AF XY:

0.481

AC XY:

349755

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.867

AC:

29034

AN:

33478

American (AMR)

AF:

0.326

AC:

14580

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

10474

AN:

26136

East Asian (EAS)

AF:

0.451

AC:

17908

AN:

39696

South Asian (SAS)

AF:

0.482

AC:

41576

AN:

86258

European-Finnish (FIN)

AF:

0.420

AC:

22402

AN:

53336

Middle Eastern (MID)

AF:

0.432

AC:

2490

AN:

5768

European-Non Finnish (NFE)

AF:

0.482

AC:

536415

AN:

1111962

Other (OTH)

AF:

0.492

AC:

29726

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

24097

48194

72290

96387

120484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15880

31760

47640

63520

79400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.561

AC:

85338

AN:

152098

Hom.:

26559

Cov.:

AF XY:

0.551

AC XY:

40961

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.847

AC:

35195

AN:

41542

American (AMR)

AF:

0.404

AC:

6173

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1411

AN:

3472

East Asian (EAS)

AF:

0.426

AC:

2204

AN:

5170

South Asian (SAS)

AF:

0.484

AC:

2330

AN:

4818

European-Finnish (FIN)

AF:

0.402

AC:

4257

AN:

10584

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.474

AC:

32208

AN:

67926

Other (OTH)

AF:

0.523

AC:

1107

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1665

3329

4994

6658

8323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.498

Hom.:

80364

Bravo

AF:

0.571

TwinsUK

AF:

0.491

AC:

1822

ALSPAC

AF:

0.476

AC:

1834

ESP6500AA

AF:

0.840

AC:

3701

ESP6500EA

AF:

0.472

AC:

4059

ExAC

AF:

0.479

AC:

58212

Asia WGS

AF:

0.453

AC:

1577

AN:

3478

EpiCase

AF:

0.465

EpiControl

AF:

0.468

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.089

DEOGEN2

Benign

0.26

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.048

MetaRNN

Benign

0.0000032

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

1.3

PrimateAI

Benign

0.42

PROVEAN

Benign

0.42

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.052

MPC

0.60

ClinPred

0.00049

GERP RS

2.9

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.10

gMVP

0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over