chr16-3965993-C-T
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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
NM_001116.4 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 5.97
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]
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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 |
---|---|---|---|---|---|---|---|
ADCY9 | NM_001116.4 | c.3844G>A | p.Val1282Met | missense_variant | 11/11 | ENST00000294016.8 | |
ADCY9 | XM_005255079.4 | c.3901G>A | p.Val1301Met | missense_variant | 11/11 | ||
ADCY9 | XM_011522353.3 | c.2927+8676G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY9 | ENST00000294016.8 | c.3844G>A | p.Val1282Met | missense_variant | 11/11 | 1 | NM_001116.4 | P1 | |
ADCY9 | ENST00000576936.5 | c.567+8676G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251466Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135918
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GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000798 AC XY: 58AN XY: 727248
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74336
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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 submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at