Variant 3-123448242-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_183357.3(ADCY5):c.304G>T(p.Ala102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADCY5
NM_183357.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ADCY5. . Gene score misZ 3.4043 (greater than the threshold 3.09). Trascript score misZ 4.4657 (greater than threshold 3.09). GenCC has associacion of gene with dyskinesia with orofacial involvement, autosomal dominant, neurodevelopmental disorder with hyperkinetic movements and dyskinesia, choreatic disease, familial dyskinesia and facial myokymia.

BP4

Computational evidence support a benign effect (MetaRNN=0.22588158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY5	NM_183357.3 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	1/21	ENST00000462833.6	NP_899200.1
ADCY5	NM_001378259.1 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	1/22		NP_001365188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY5	ENST00000462833.6 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	1/21	1	NM_183357.3	ENSP00000419361	P1	O95622-1
ADCY5	ENST00000699718.1 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	1/22			ENSP00000514543

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1296098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

640610

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.66

REVEL

Benign

0.20

Sift

Uncertain

0.014

Sift4G

Uncertain

0.029

Polyphen

0.0010

Vest4

0.21

MutPred

0.17

Gain of glycosylation at S101 (P = 0.0069);

MVP

0.57

MPC

0.81

ClinPred

0.48

GERP RS

1.9

Varity_R

0.20

gMVP

0.33

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over