2-24823221-TGA-GCT

Variant names:

• chr2-24823221-TGA-GCT
• NM_004036.5:c.2869_2871delTCAinsAGC
• ADCY3 p.958

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004036.5(ADCY3):​c.2869_2871delTCAinsAGC​(p.958) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S957S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY3 NM_004036.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.97
• Publications: 0 publications found

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]

ADCY3 Gene-Disease associations (from GenCC):

• body mass index quantitative trait locus 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004036.5. 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
	ADCY3	NM_004036.5	MANE Select	c.2869_2871delTCAinsAGC	p.958	synonymous	N/A	NP_004027.2	O60266-1
	ADCY3	NM_001377128.1		c.2935_2937delTCAinsAGC	p.980	synonymous	N/A	NP_001364057.1
	ADCY3	NM_001320613.2		c.2872_2874delTCAinsAGC	p.959	synonymous	N/A	NP_001307542.1	A0A0A0MSC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY3	ENST00000679454.1	MANE Select	c.2869_2871delTCAinsAGC	p.958	synonymous	N/A	ENSP00000505261.1	O60266-1
	ADCY3	ENST00000405392.6	TSL:1	c.2872_2874delTCAinsAGC	p.959	synonymous	N/A	ENSP00000384484.2	A0A0A0MSC1
	ADCY3	ENST00000260600.9	TSL:1	c.2869_2871delTCAinsAGC	p.958	synonymous	N/A	ENSP00000260600.5	O60266-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-25046090;