rs982000290

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001198568.2(ADCY4):​c.2825G>C​(p.Gly942Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G942E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ADCY4
NM_001198568.2 missense

Scores

6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.00
Variant links:
Genes affected
ADCY4 (HGNC:235): (adenylate cyclase 4) This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). Mouse studies show that adenylate cyclase 4, along with adenylate cyclases 2 and 3, is expressed in olfactory cilia, suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.29286045).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADCY4NM_001198568.2 linkc.2825G>C p.Gly942Ala missense_variant Exon 22 of 25 ENST00000418030.7 NP_001185497.1 Q8NFM4-1
ADCY4NM_001198592.2 linkc.2825G>C p.Gly942Ala missense_variant Exon 23 of 26 NP_001185521.1 Q8NFM4-1Q86TZ7
ADCY4NM_139247.4 linkc.2825G>C p.Gly942Ala missense_variant Exon 23 of 26 NP_640340.2 Q8NFM4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADCY4ENST00000418030.7 linkc.2825G>C p.Gly942Ala missense_variant Exon 22 of 25 1 NM_001198568.2 ENSP00000393177.2 Q8NFM4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727244
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;D;D
Eigen
Benign
0.055
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Benign
0.16
Sift
Benign
0.077
T;T;T
Sift4G
Benign
0.076
T;T;T
Polyphen
0.060
B;B;B
Vest4
0.36
MutPred
0.54
Gain of catalytic residue at N938 (P = 0.0241);Gain of catalytic residue at N938 (P = 0.0241);Gain of catalytic residue at N938 (P = 0.0241);
MVP
0.75
MPC
1.1
ClinPred
0.86
D
GERP RS
5.8
Varity_R
0.21
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

hg19: chr14-24788551; API