rs11717195

Variant names:

• chr3-123363551-T-C
• rs11717195
• NM_183357.3:c.1135-10970A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183357.3(ADCY5):​c.1135-10970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,230 control chromosomes in the GnomAD database, including 2,919 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 0.18 (2919 hom., cov: 33)
• Consequence: ADCY5 NM_183357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888
• Publications: 76 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY5	NM_183357.3	MANE Select	c.1135-10970A>G		intron	N/A	NP_899200.1	O95622-1
	ADCY5	NM_001378259.1		c.1135-10970A>G		intron	N/A	NP_001365188.1	A0A8V8TP58
	ADCY5	NM_001199642.1		c.85-10970A>G		intron	N/A	NP_001186571.1	O95622-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY5	ENST00000462833.6	TSL:1 MANE Select	c.1135-10970A>G		intron	N/A	ENSP00000419361.1	O95622-1
	ADCY5	ENST00000850916.1		c.1297-10970A>G		intron	N/A	ENSP00000520999.1	A0ABJ7H376
	ADCY5	ENST00000699718.1		c.1135-10970A>G		intron	N/A	ENSP00000514543.1	A0A8V8TP58

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28088 AN: 152112 Hom.: 2916 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.185 AC: 28100 AN: 152230 Hom.: 2919 Cov.: 33 AF XY: 0.182 AC XY: 13525 AN XY: 74416

African (AFR) AF: 0.114 AC: 4743 AN: 41534

American (AMR) AF: 0.256 AC: 3922 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.201 AC: 970 AN: 4830

European-Finnish (FIN) AF: 0.168 AC: 1784 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15543 AN: 68008

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.205 Hom.: 5636

Bravo AF: 0.186

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.71
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs11717195;

hg19: chr3-123082398;