NM_021116.4:c.3112C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_021116.4(ADCY1):c.3112C>T(p.Arg1038*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 628,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
ADCY1
NM_021116.4 stop_gained
NM_021116.4 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 1.96
Publications
5 publications found
Genes affected
ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
ADCY1 Gene-Disease associations (from GenCC):
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
- autosomal recessive nonsyndromic hearing loss 44Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0738 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000159 AC: 1AN: 628452Hom.: 0 Cov.: 0 AF XY: 0.00000292 AC XY: 1AN XY: 342378 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
628452
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
342378
show subpopulations
African (AFR)
AF:
AC:
0
AN:
17694
American (AMR)
AF:
AC:
0
AN:
43740
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
20982
East Asian (EAS)
AF:
AC:
0
AN:
36070
South Asian (SAS)
AF:
AC:
1
AN:
69798
European-Finnish (FIN)
AF:
AC:
0
AN:
52824
Middle Eastern (MID)
AF:
AC:
0
AN:
4148
European-Non Finnish (NFE)
AF:
AC:
0
AN:
350108
Other (OTH)
AF:
AC:
0
AN:
33088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: no classifications from unflagged records
Submissions summary: Pathogenic:2
Revision: no classifications from unflagged records
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 44 Pathogenic:2
Nov 20, 2014
Department of Molecular and Human Genetics, Baylor College of Medicine
Significance:Pathogenic
Review Status:flagged submission
Collection Method:research
- -
Jun 15, 2014
OMIM
Significance:Pathogenic
Review Status:flagged submission
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
ClinPred
D
GERP RS
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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