chr2-24839959-GC-G
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001377128.1(ADCY3):c.1268delG(p.Gly423AlafsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as risk factor (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ADCY3
NM_001377128.1 frameshift
NM_001377128.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.90
Publications
3 publications found
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 Gene-Disease associations (from GenCC):
- body mass index quantitative trait locus 19Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001377128.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ADCY3 | NM_004036.5 | MANE Select | c.1268delG | p.Gly423AlafsTer19 | frameshift | Exon 7 of 22 | NP_004027.2 | ||
| ADCY3 | NM_001377128.1 | c.1268delG | p.Gly423AlafsTer19 | frameshift | Exon 7 of 23 | NP_001364057.1 | |||
| ADCY3 | NM_001320613.2 | c.1268delG | p.Gly423AlafsTer19 | frameshift | Exon 7 of 22 | NP_001307542.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ADCY3 | ENST00000679454.1 | MANE Select | c.1268delG | p.Gly423AlafsTer19 | frameshift | Exon 7 of 22 | ENSP00000505261.1 | ||
| ADCY3 | ENST00000405392.6 | TSL:1 | c.1268delG | p.Gly423AlafsTer19 | frameshift | Exon 6 of 21 | ENSP00000384484.2 | ||
| ADCY3 | ENST00000260600.9 | TSL:1 | c.1268delG | p.Gly423AlafsTer19 | frameshift | Exon 6 of 21 | ENSP00000260600.5 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152174
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461500Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727036 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461500
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727036
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53066
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1111988
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74324 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152174
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74324
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41444
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5182
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68032
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:risk factor
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
-
-
BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 19 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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