chr3-123284660-CCCTTGA-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM4PP3
The NM_183357.3(ADCY5):c.3728_3733del(p.Val1243_Lys1244del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
ADCY5
NM_183357.3 inframe_deletion
NM_183357.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.97
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 Uncertain_significance. Variant got 3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_183357.3.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADCY5 | NM_183357.3 | c.3728_3733del | p.Val1243_Lys1244del | inframe_deletion | 21/21 | ENST00000462833.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY5 | ENST00000462833.6 | c.3728_3733del | p.Val1243_Lys1244del | inframe_deletion | 21/21 | 1 | NM_183357.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461884Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727246
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with ADCY5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant, c.3728_3733del, results in the deletion of 2 amino acid(s) of the ADCY5 protein (p.Val1243_Lys1244del), but otherwise preserves the integrity of the reading frame. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at