3-123448117-AGCCGCCGCCGCCGAGCCGCC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_183357.3(ADCY5):c.409_428del(p.Gly137CysfsTer184) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 948,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000011 ( 0 hom. )
Consequence
ADCY5
NM_183357.3 frameshift
NM_183357.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.90
Genes affected
ADCY5 (HGNC:236): (adenylate cyclase 5) This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 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 3-123448117-AGCCGCCGCCGCCGAGCCGCC-A is Pathogenic according to our data. Variant chr3-123448117-AGCCGCCGCCGCCGAGCCGCC-A is described in ClinVar as [Pathogenic]. Clinvar id is 521036.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADCY5 | NM_183357.3 | c.409_428del | p.Gly137CysfsTer184 | frameshift_variant | 1/21 | ENST00000462833.6 | |
ADCY5 | NM_001378259.1 | c.409_428del | p.Gly137CysfsTer184 | frameshift_variant | 1/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY5 | ENST00000462833.6 | c.409_428del | p.Gly137CysfsTer184 | frameshift_variant | 1/21 | 1 | NM_183357.3 | P1 | |
ADCY5 | ENST00000699718.1 | c.409_428del | p.Gly137CysfsTer184 | frameshift_variant | 1/22 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000105 AC: 1AN: 948302Hom.: 0 AF XY: 0.00000222 AC XY: 1AN XY: 449970
GnomAD4 exome
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1
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2019 | - - |
Dyskinesia with orofacial involvement, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 09, 2021 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at