Variant 2-24823221-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004036.5(ADCY3):c.2871A>G(p.Ser957=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,611,864 control chromosomes in the GnomAD database, including 371,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 32642 hom., cov: 32)

Exomes 𝑓: 0.68 ( 338768 hom. )

Consequence

ADCY3
NM_004036.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.32

Variant links:

Genes affected

ADCY3 (HGNC:234): (adenylate cyclase 3) This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ADCY3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 2-24823221-T-C is Benign according to our data. Variant chr2-24823221-T-C is described in ClinVar as [Benign]. Clinvar id is 1641173.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY3	NM_004036.5 linkuse as main transcript	c.2871A>G	p.Ser957=	synonymous_variant	18/22	ENST00000679454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY3	ENST00000679454.1 linkuse as main transcript	c.2871A>G	p.Ser957=	synonymous_variant	18/22		NM_004036.5	P4	O60266-1

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98760

AN:

151934

Hom.:

32628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.875

Gnomad SAS

AF:

0.693

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.684

GnomAD3 exomes

AF:

0.694

AC:

173780

AN:

250322

Hom.:

61392

AF XY:

0.690

AC XY:

93392

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.533

Gnomad AMR exome

AF:

0.849

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.854

Gnomad SAS exome

AF:

0.675

Gnomad FIN exome

AF:

0.660

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.700

GnomAD4 exome

AF:

0.679

AC:

991473

AN:

1459812

Hom.:

338768

Cov.:

AF XY:

0.679

AC XY:

492699

AN XY:

726138

show subpopulations

Gnomad4 AFR exome

AF:

0.523

Gnomad4 AMR exome

AF:

0.841

Gnomad4 ASJ exome

AF:

0.658

Gnomad4 EAS exome

AF:

0.877

Gnomad4 SAS exome

AF:

0.677

Gnomad4 FIN exome

AF:

0.656

Gnomad4 NFE exome

AF:

0.672

Gnomad4 OTH exome

AF:

0.687

GnomAD4 genome

AF:

0.650

AC:

98817

AN:

152052

Hom.:

32642

Cov.:

AF XY:

0.654

AC XY:

48611

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.535

Gnomad4 AMR

AF:

0.774

Gnomad4 ASJ

AF:

0.643

Gnomad4 EAS

AF:

0.875

Gnomad4 SAS

AF:

0.693

Gnomad4 FIN

AF:

0.654

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.687

Alfa

AF:

0.665

Hom.:

53623

Bravo

AF:

0.657

Asia WGS

AF:

0.780

AC:

2713

AN:

3478

EpiCase

AF:

0.664

EpiControl

AF:

0.676

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.058

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over