rs1554123960
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_006586.5(CNPY3):c.702_720dup(p.Ser241GlyfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CNPY3
NM_006586.5 frameshift
NM_006586.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.56
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.162 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-42938655-A-AGGCAGCAGGCGGCAGGAGT is Pathogenic according to our data. Variant chr6-42938655-A-AGGCAGCAGGCGGCAGGAGT is described in ClinVar as [Pathogenic]. Clinvar id is 518430.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNPY3 | NM_006586.5 | c.702_720dup | p.Ser241GlyfsTer7 | frameshift_variant | 6/6 | ENST00000372836.5 | NP_006577.2 | |
CNPY3-GNMT | NR_134890.2 | n.339+2986_339+3004dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNPY3 | ENST00000372836.5 | c.702_720dup | p.Ser241GlyfsTer7 | frameshift_variant | 6/6 | 1 | NM_006586.5 | ENSP00000361926 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460866Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726620
GnomAD4 exome
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4
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1460866
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32
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3
AN XY:
726620
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 60 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 17, 2020 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at