rs13317079

Variant names:

• chr3-123284451-C-A
• rs13317079
• NM_183357.3:c.*157G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-123284451-C-A
• chr3-123284451-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_183357.3(ADCY5):​c.*157G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,234,800 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (32 hom.)
• Consequence: ADCY5 NM_183357.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.420
• Publications: 6 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, 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: Ambry Genetics, Orphanet
• choreatic disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-123284451-C-A is Benign according to our data. Variant chr3-123284451-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1197518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2087/152370) while in subpopulation AFR AF = 0.0461 (1919/41588). AF 95% confidence interval is 0.0444. There are 47 homozygotes in GnomAd4. There are 956 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY5	NM_183357.3	c.*157G>T		3_prime_UTR_variant	Exon 21 of 21	ENST00000462833.6	NP_899200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6	c.*157G>T		3_prime_UTR_variant	Exon 21 of 21	1	NM_183357.3	ENSP00000419361.1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2088 AN: 152252 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00817

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00155 AC: 1683 AN: 1082430 Hom.: 32 Cov.: 15 AF XY: 0.00138 AC XY: 740 AN XY: 534320

African (AFR) AF: 0.0489 AC: 1202 AN: 24580

American (AMR) AF: 0.00349 AC: 79 AN: 22668

Ashkenazi Jewish (ASJ) AF: 0.0000560 AC: 1 AN: 17854

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35062

South Asian (SAS) AF: 0.0000978 AC: 6 AN: 61328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32520

Middle Eastern (MID) AF: 0.00474 AC: 15 AN: 3166

European-Non Finnish (NFE) AF: 0.000248 AC: 208 AN: 838414

Other (OTH) AF: 0.00365 AC: 171 AN: 46838

GnomAD4 genome AF: 0.0137 AC: 2087 AN: 152370 Hom.: 47 Cov.: 33 AF XY: 0.0128 AC XY: 956 AN XY: 74510

African (AFR) AF: 0.0461 AC: 1919 AN: 41588

American (AMR) AF: 0.00816 AC: 125 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68040

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00877 Hom.: 41

Bravo AF: 0.0156

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism

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: rs13317079; hg19: chr3-123003298;