12-48768609-ATT-GGA

Variant names:

• chr12-48768609-ATT-GGA
• NM_015270.5:c.3487_3489delAATinsTCC
• ADCY6 p.Asn1163Ser

Variant summary

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

The NM_015270.5(ADCY6):​c.3487_3489delAATinsTCC​(p.Asn1163Ser) variant causes a missense change. 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. N1163I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY6 NM_015270.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21
• Publications: 0 publications found

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]

SPMIP11 (HGNC:48628): (sperm microtubule inner protein 11)

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY6	NM_015270.5	MANE Select	c.3487_3489delAATinsTCC	p.Asn1163Ser	missense	N/A	NP_056085.1	O43306-1
	ADCY6	NM_001390831.2		c.3487_3489delAATinsTCC	p.Asn1163Ser	missense	N/A	NP_001377760.1	O43306-1
	ADCY6	NM_001412819.1		c.3487_3489delAATinsTCC	p.Asn1163Ser	missense	N/A	NP_001399748.1	O43306-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY6	ENST00000357869.8	TSL:2 MANE Select	c.3487_3489delAATinsTCC	p.Asn1163Ser	missense	N/A	ENSP00000350536.4	O43306-1
	ADCY6	ENST00000307885.4	TSL:1	c.3487_3489delAATinsTCC	p.Asn1163Ser	missense	N/A	ENSP00000311405.4	O43306-1
	ADCY6	ENST00000960700.1		c.3568_3570delAATinsTCC	p.Asn1190Ser	missense	N/A	ENSP00000630759.1

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		6.2

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: chr12-49162392;