chr1-167880124-CGT-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018417.6(ADCY10):c.1205_1206delAC(p.His402ArgfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. H402H) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ADCY10
NM_018417.6 frameshift
NM_018417.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.46
Publications
1 publications found
Genes affected
ADCY10 (HGNC:21285): (adenylate cyclase 10) The protein encoded by this gene belongs to a distinct class of adenylyl cyclases that is soluble and insensitive to G protein or forskolin regulation. Activity of this protein is regulated by bicarbonate. Variation at this gene has been observed in patients with absorptive hypercalciuria. Alternatively spliced transcript variants encoding different isoforms have been observed. There is a pseudogene of this gene on chromosome 6. [provided by RefSeq, Jul 2014]
DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 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;
PP5
Variant 1-167880124-CGT-C is Pathogenic according to our data. Variant chr1-167880124-CGT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 544683.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018417.6. 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 |
|---|---|---|---|---|---|---|---|---|---|
| ADCY10 | NM_018417.6 | MANE Select | c.1205_1206delAC | p.His402ArgfsTer41 | frameshift | Exon 11 of 33 | NP_060887.2 | ||
| ADCY10 | NM_001297772.2 | c.929_930delAC | p.His310ArgfsTer41 | frameshift | Exon 11 of 33 | NP_001284701.1 | |||
| ADCY10 | NM_001167749.3 | c.746_747delAC | p.His249ArgfsTer41 | frameshift | Exon 8 of 30 | NP_001161221.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ADCY10 | ENST00000367851.9 | TSL:1 MANE Select | c.1205_1206delAC | p.His402ArgfsTer41 | frameshift | Exon 11 of 33 | ENSP00000356825.4 | ||
| ADCY10 | ENST00000367848.1 | TSL:1 | c.929_930delAC | p.His310ArgfsTer41 | frameshift | Exon 11 of 33 | ENSP00000356822.1 | ||
| ADCY10 | ENST00000545172.5 | TSL:2 | c.746_747delAC | p.His249ArgfsTer41 | frameshift | Exon 8 of 30 | ENSP00000441992.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000403 AC: 1AN: 248422 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
248422
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1459940Hom.: 0 AF XY: 0.00000276 AC XY: 2AN XY: 725938 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1459940
Hom.:
AF XY:
AC XY:
2
AN XY:
725938
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33456
American (AMR)
AF:
AC:
0
AN:
44510
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26080
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
85506
European-Finnish (FIN)
AF:
AC:
0
AN:
53346
Middle Eastern (MID)
AF:
AC:
0
AN:
5650
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111358
Other (OTH)
AF:
AC:
0
AN:
60336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Abnormal sperm morphology;C4082176:Reduced sperm motility (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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