chr3-123346931-A-G

Variant names:

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_183357.3(ADCY5):c.1406+851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,998 control chromosomes in the GnomAD database, including 3,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3061 hom., cov: 31)

Consequence

ADCY5
NM_183357.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

Publications

247 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, SD Classification: STRONG Submitted by: G2P, PanelApp Australia
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: Ambry Genetics, Orphanet
choreatic disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADCY5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_183357.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
ADCY5	NM_183357.3	MANE Select	c.1406+851T>C	intron	N/A	NP_899200.1	O95622-1
ADCY5	NM_001378259.1		c.1406+851T>C	intron	N/A	NP_001365188.1	A0A8V8TP58
ADCY5	NM_001199642.1		c.356+851T>C	intron	N/A	NP_001186571.1	O95622-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCY5	ENST00000462833.6	TSL:1 MANE Select	c.1406+851T>C	intron	N/A	ENSP00000419361.1	O95622-1
ADCY5	ENST00000850916.1		c.1568+851T>C	intron	N/A	ENSP00000520999.1	A0ABJ7H376
ADCY5	ENST00000699718.1		c.1406+851T>C	intron	N/A	ENSP00000514543.1	A0A8V8TP58

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29294

AN:

151878

Hom.:

3057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.193

AC:

29310

AN:

151998

Hom.:

3061

Cov.:

AF XY:

0.189

AC XY:

14066

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.151

AC:

6258

AN:

41470

American (AMR)

AF:

0.261

AC:

3986

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

569

AN:

3468

East Asian (EAS)

AF:

0.00271

AC:

AN:

5164

South Asian (SAS)

AF:

0.199

AC:

956

AN:

4812

European-Finnish (FIN)

AF:

0.161

AC:

1701

AN:

10550

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15269

AN:

67948

Other (OTH)

AF:

0.162

AC:

341

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1217

2434

3652

4869

6086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.208

Hom.:

14631

Bravo

AF:

0.196

Asia WGS

AF:

0.0960

AC:

332

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over