3-123412407-C-T

Variant names:

• chr3-123412407-C-T
• rs17361324
• NM_183357.3:c.1134+35005G>A

Variant summary

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

The NM_183357.3(ADCY5):​c.1134+35005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,186 control chromosomes in the GnomAD database, including 3,403 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 0.20 (3403 hom., cov: 32)
• Consequence: ADCY5 NM_183357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 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.1134+35005G>A		intron	N/A	NP_899200.1	O95622-1
	ADCY5	NM_001378259.1		c.1134+35005G>A		intron	N/A	NP_001365188.1	A0A8V8TP58
	ADCY5	NM_001199642.1		c.84+3777G>A		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.1134+35005G>A		intron	N/A	ENSP00000419361.1	O95622-1
	ADCY5	ENST00000850916.1		c.1296+35005G>A		intron	N/A	ENSP00000520999.1	A0ABJ7H376
	ADCY5	ENST00000699718.1		c.1134+35005G>A		intron	N/A	ENSP00000514543.1	A0A8V8TP58

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30329 AN: 152068 Hom.: 3400 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.199 AC: 30343 AN: 152186 Hom.: 3403 Cov.: 32 AF XY: 0.196 AC XY: 14609 AN XY: 74434

African (AFR) AF: 0.118 AC: 4883 AN: 41512

American (AMR) AF: 0.272 AC: 4164 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5180

South Asian (SAS) AF: 0.204 AC: 981 AN: 4818

European-Finnish (FIN) AF: 0.183 AC: 1943 AN: 10604

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17043 AN: 67988

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.215 Hom.: 3869

Bravo AF: 0.200

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.45
PhyloP100		-0.057
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

Other links and lift over

dbSNP: rs17361324; hg19: chr3-123131254;