15-34038849-TCG-CCC

Variant names:

• chr15-34038849-TCG-CCC
• NM_020371.3:c.196_198delCGAinsGGG
• AVEN p.Arg66Gly

Variant summary

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

The NM_020371.3(AVEN):​c.196_198delCGAinsGGG​(p.Arg66Gly) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R66Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AVEN NM_020371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 0 publications found

Genes affected

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHRM5 (HGNC:1954): (cholinergic receptor muscarinic 5) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020371.3. 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
	AVEN	NM_020371.3	MANE Select	c.196_198delCGAinsGGG	p.Arg66Gly	missense	N/A	NP_065104.1	Q9NQS1
	CHRM5	NM_012125.4	MANE Select	c.-407-7691_-407-7689delTCGinsCCC		intron	N/A	NP_036257.1	P08912
	CHRM5	NM_001320917.2		c.-75-23794_-75-23792delTCGinsCCC		intron	N/A	NP_001307846.1	P08912

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVEN	ENST00000306730.8	TSL:1 MANE Select	c.196_198delCGAinsGGG	p.Arg66Gly	missense	N/A	ENSP00000306822.3	Q9NQS1
	CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-407-7691_-407-7689delTCGinsCCC		intron	N/A	ENSP00000372750.5	P08912
	CHRM5	ENST00000557872.1	TSL:1	c.-76+20384_-76+20386delTCGinsCCC		intron	N/A	ENSP00000453745.1	P08912

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		0.47

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: chr15-34331050;