6-42929619-TTGCTGCTGCTGCTGCTGC-T

Variant names:

• chr6-42929619-TTGCTGCTGCTGCTGCTGC-T
• rs570105218
• NM_006586.5:c.59_76delTGCTGCTGCTGCTGCTGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_006586.5(CNPY3):​c.59_76delTGCTGCTGCTGCTGCTGC​(p.Leu20_Leu25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,520 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CNPY3 NM_006586.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_006586.5

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.59_76delTGCTGCTGCTGCTGCTGC	p.Leu20_Leu25del	disruptive_inframe_deletion	Exon 1 of 6	NP_006577.2
	CNPY3	NM_001318842.1		c.59_76delTGCTGCTGCTGCTGCTGC	p.Leu20_Leu25del	disruptive_inframe_deletion	Exon 1 of 7	NP_001305771.1
	CNPY3-GNMT	NM_001318857.2		c.59_76delTGCTGCTGCTGCTGCTGC	p.Leu20_Leu25del	disruptive_inframe_deletion	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.59_76delTGCTGCTGCTGCTGCTGC	p.Leu20_Leu25del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000361926.4	Q9BT09-1
	CNPY3	ENST00000893179.1		c.59_76delTGCTGCTGCTGCTGCTGC	p.Leu20_Leu25del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000563238.1
	CNPY3	ENST00000924680.1		c.59_76delTGCTGCTGCTGCTGCTGC	p.Leu20_Leu25del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000594739.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408520 Hom.: 0 AF XY: 0.00000144 AC XY: 1 AN XY: 696218

African (AFR) AF: 0.0000309 AC: 1 AN: 32322

American (AMR) AF: 0.00 AC: 0 AN: 36694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25260

East Asian (EAS) AF: 0.00 AC: 0 AN: 36984

South Asian (SAS) AF: 0.00 AC: 0 AN: 80482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085236

Other (OTH) AF: 0.00 AC: 0 AN: 58420

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=84/116	disease causing (long InDel)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs570105218; hg19: chr6-42897357;