2-24820835-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_004036.5(ADCY3):c.3141C>T(p.Gly1047=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,918 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
ADCY3
NM_004036.5 synonymous
NM_004036.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.92
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]
CENPO (HGNC:28152): (centromere protein O) This gene encodes a component of the interphase centromere complex. The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 2-24820835-G-A is Benign according to our data. Variant chr2-24820835-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1634482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.92 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADCY3 | NM_004036.5 | c.3141C>T | p.Gly1047= | synonymous_variant | 21/22 | ENST00000679454.1 | |
CENPO | NM_001322101.2 | c.*1517G>A | 3_prime_UTR_variant | 8/8 | ENST00000380834.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY3 | ENST00000679454.1 | c.3141C>T | p.Gly1047= | synonymous_variant | 21/22 | NM_004036.5 | P4 | ||
CENPO | ENST00000380834.7 | c.*1517G>A | 3_prime_UTR_variant | 8/8 | 5 | NM_001322101.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152032Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251246Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135782
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461768Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17AN XY: 727186
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74398
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
ADCY3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 07, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at