NM_006586.5:c.65_76dupTGCTGCTGCTGC

Variant names:

• chr6-42929618-CT-CTTGCTGCTGCTG
• NM_006586.5:c.50_60dupTGCTGCTGCTG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_006586.5(CNPY3):​c.50_60dupTGCTGCTGCTG​(p.Leu21CysfsTer43) variant causes a frameshift 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 INS_BIG, 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. Synonymous variant affecting the same amino acid position (i.e. L21L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNPY3 NM_006586.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• Publications: 0 publications found

Genes affected

CNPY3 (HGNC:11968): (canopy FGF signaling regulator 3) This gene encodes a protein that binds members of the toll-like receptor protein family and functions as a chaperone to aid in folding and export of these proteins. Alternative splicing results in multiple transcript variants. Naturally occuring readthrough transcription occurs between this locus and the downstream GNMT (glycine N-methyltransferase) gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

CNPY3 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 60

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CNPY3-GNMT (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006586.5. 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
	CNPY3	NM_006586.5	MANE Select	c.50_60dupTGCTGCTGCTG	p.Leu21CysfsTer43	frameshift	Exon 1 of 6	NP_006577.2
	CNPY3	NM_001318842.1		c.50_60dupTGCTGCTGCTG	p.Leu21CysfsTer43	frameshift	Exon 1 of 7	NP_001305771.1
	CNPY3-GNMT	NM_001318857.2		c.50_60dupTGCTGCTGCTG	p.Leu21CysfsTer42	frameshift	Exon 1 of 5	NP_001305786.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNPY3	ENST00000372836.5	TSL:1 MANE Select	c.50_60dupTGCTGCTGCTG	p.Leu21CysfsTer43	frameshift	Exon 1 of 6	ENSP00000361926.4	Q9BT09-1
	CNPY3	ENST00000893179.1		c.50_60dupTGCTGCTGCTG	p.Leu21CysfsTer43	frameshift	Exon 1 of 6	ENSP00000563238.1
	CNPY3	ENST00000924680.1		c.50_60dupTGCTGCTGCTG	p.Leu21CysfsTer74	frameshift	Exon 1 of 7	ENSP00000594739.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42

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: chr6-42897356;