rs141058563

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_183357.3(ADCY5):c.3684G>A(p.Leu1228Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,614,256 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ADCY5
NM_183357.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.99

Publications

1 publications found

Variant links:

Genes affected

ADCY5 (HGNC:236): (adenylate cyclase 5) This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ADCY5 Gene-Disease associations (from GenCC):

dyskinesia with orofacial involvement
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
dyskinesia with orofacial involvement, autosomal dominant
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: G2P
neurodevelopmental disorder with hyperkinetic movements and dyskinesia
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
familial dyskinesia and facial myokymia
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
choreatic disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADCY5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-123284710-C-T is Benign according to our data. Variant chr3-123284710-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 425304.

BP7

Synonymous conserved (PhyloP=1.99 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183357.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY5	NM_183357.3	MANE Select	c.3684G>A	p.Leu1228Leu	synonymous	Exon 21 of 21	NP_899200.1	O95622-1
ADCY5	NM_001378259.1		c.3759G>A	p.Leu1253Leu	synonymous	Exon 22 of 22	NP_001365188.1	A0A8V8TP58
ADCY5	NM_001199642.1		c.2634G>A	p.Leu878Leu	synonymous	Exon 21 of 21	NP_001186571.1	O95622-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY5	ENST00000462833.6	TSL:1 MANE Select	c.3684G>A	p.Leu1228Leu	synonymous	Exon 21 of 21	ENSP00000419361.1	O95622-1
ADCY5	ENST00000850916.1		c.3846G>A	p.Leu1282Leu	synonymous	Exon 21 of 21	ENSP00000520999.1	A0ABJ7H376
ADCY5	ENST00000699718.1		c.3759G>A	p.Leu1253Leu	synonymous	Exon 22 of 22	ENSP00000514543.1	A0A8V8TP58

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000143

AC:

AN:

251468

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000191

AC:

279

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000201

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000234

AC:

260

AN:

1112004

Other (OTH)

AF:

0.000116

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000131

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41586

American (AMR)

AF:

0.000261

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000307

Hom.:

Bravo

AF:

0.000200

EpiCase

AF:

0.000491

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.0

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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