chr16-3965993-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001116.4(ADCY9):​c.3844G>A​(p.Val1282Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

ADCY9
NM_001116.4 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97
Variant links:
Genes affected
ADCY9 (HGNC:240): (adenylate cyclase 9) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, calcium, and somatostatin. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADCY9NM_001116.4 linkuse as main transcriptc.3844G>A p.Val1282Met missense_variant 11/11 ENST00000294016.8
ADCY9XM_005255079.4 linkuse as main transcriptc.3901G>A p.Val1301Met missense_variant 11/11
ADCY9XM_011522353.3 linkuse as main transcriptc.2927+8676G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADCY9ENST00000294016.8 linkuse as main transcriptc.3844G>A p.Val1282Met missense_variant 11/111 NM_001116.4 P1
ADCY9ENST00000576936.5 linkuse as main transcriptc.567+8676G>A intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251466
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000691
AC:
101
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.0000798
AC XY:
58
AN XY:
727248
show subpopulations
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:
0.0000187
Gnomad4 NFE exome
AF:
0.0000854
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000965
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2023The c.3844G>A (p.V1282M) alteration is located in exon 11 (coding exon 10) of the ADCY9 gene. This alteration results from a G to A substitution at nucleotide position 3844, causing the valine (V) at amino acid position 1282 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.26
T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.69
D
MetaSVM
Uncertain
0.16
D
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.81
N
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.61
MVP
0.71
MPC
1.3
ClinPred
0.82
D
GERP RS
5.8
Varity_R
0.27
gMVP
0.43

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.

Other links and lift over

dbSNP: rs375515956; hg19: chr16-4015994; API