NM_021116.4:c.262_264delCCCinsTTA

Variant names:

• chr7-45574805-CCC-TTA
• NM_021116.4:c.262_264delCCCinsTTA
• ADCY1 p.Pro88Leu

Variant summary

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

The NM_021116.4(ADCY1):​c.262_264delCCCinsTTA​(p.Pro88Leu) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P88P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY1 NM_021116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ADCY1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 44

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021116.4. 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
	ADCY1	NM_021116.4	MANE Select	c.262_264delCCCinsTTA	p.Pro88Leu	missense	N/A	NP_066939.1	Q08828
	ADCY1	NM_001281768.2		c.-330-84_-330-82delCCCinsTTA		intron	N/A	NP_001268697.1	C9J1J0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY1	ENST00000297323.12	TSL:1 MANE Select	c.262_264delCCCinsTTA	p.Pro88Leu	missense	N/A	ENSP00000297323.7	Q08828
	ADCY1	ENST00000920696.1		c.262_264delCCCinsTTA	p.Pro88Leu	missense	N/A	ENSP00000590755.1
	ADCY1	ENST00000432715.5	TSL:2	c.-330-84_-330-82delCCCinsTTA		intron	N/A	ENSP00000392721.1	C9J1J0

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		1.1

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: chr7-45614404;