14-24319763-CTC-TTT

Variant names:

• chr14-24319763-CTC-TTT
• NM_001198568.2:c.2710_2712delGAGinsAAA
• ADCY4 p.Glu904Lys

Variant summary

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

The NM_001198568.2(ADCY4):​c.2710_2712delGAGinsAAA​(p.Glu904Lys) variant causes a missense 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY4 NM_001198568.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

ADCY4 (HGNC:235): (adenylate cyclase 4) This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). Mouse studies show that adenylate cyclase 4, along with adenylate cyclases 2 and 3, is expressed in olfactory cilia, suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

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_001198568.2. 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
	ADCY4	NM_001198568.2	MANE Select	c.2710_2712delGAGinsAAA	p.Glu904Lys	missense	N/A	NP_001185497.1	Q8NFM4-1
	ADCY4	NM_001198592.2		c.2710_2712delGAGinsAAA	p.Glu904Lys	missense	N/A	NP_001185521.1	Q8NFM4-1
	ADCY4	NM_139247.4		c.2710_2712delGAGinsAAA	p.Glu904Lys	missense	N/A	NP_640340.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY4	ENST00000418030.7	TSL:1 MANE Select	c.2710_2712delGAGinsAAA	p.Glu904Lys	missense	N/A	ENSP00000393177.2	Q8NFM4-1
	ADCY4	ENST00000554068.6	TSL:1	c.2710_2712delGAGinsAAA	p.Glu904Lys	missense	N/A	ENSP00000452250.2	Q8NFM4-1
	ADCY4	ENST00000554781.5	TSL:1	n.*1392_*1394delGAGinsAAA		non_coding_transcript_exon	Exon 21 of 25	ENSP00000450477.1	G3V258

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		8.0

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: chr14-24788969;