Genetic Variant ADCY6:p.Ala220Val (chr12-48782775-CG-AA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is . The variant received 0 ACMG points: 0P and 0B.

The NM_015270.5(ADCY6):c.659_660delCGinsTT(p.Ala220Val) variant causes a missense change involving the alteration of a non-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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A220E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ADCY6
NM_015270.5 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.48

Publications

0 publications found

Variant links:

Genes affected

ADCY6 (HGNC:237): (adenylate cyclase 6) This gene encodes a member of the adenylyl cyclase family of proteins, which are required for the synthesis of cyclic AMP. All members of this family have an intracellular N-terminus, a tandem repeat of six transmembrane domains separated by a cytoplasmic loop, and a C-terminal cytoplasmic domain. The two cytoplasmic regions bind ATP and form the catalytic core of the protein. Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. A mutation in this gene is associated with arthrogryposis multiplex congenita. [provided by RefSeq, May 2015]

ADCY6 Gene-Disease associations (from GenCC):

lethal congenital contracture syndrome 8
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
hypomyelination neuropathy-arthrogryposis syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ADCY6 links:

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new If you want to explore the variant's impact on the transcript NM_015270.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY6	NM_015270.5	MANE Select	c.659_660delCGinsTT	p.Ala220Val	missense	N/A	NP_056085.1	O43306-1
ADCY6	NM_001390831.2		c.659_660delCGinsTT	p.Ala220Val	missense	N/A	NP_001377760.1	O43306-1
ADCY6	NM_001412819.1		c.659_660delCGinsTT	p.Ala220Val	missense	N/A	NP_001399748.1	O43306-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY6	ENST00000357869.8	TSL:2 MANE Select	c.659_660delCGinsTT	p.Ala220Val	missense	N/A	ENSP00000350536.4	O43306-1
ADCY6	ENST00000307885.4	TSL:1	c.659_660delCGinsTT	p.Ala220Val	missense	N/A	ENSP00000311405.4	O43306-1
ADCY6	ENST00000960700.1		c.659_660delCGinsTT	p.Ala220Val	missense	N/A	ENSP00000630759.1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.5

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over