6-42935660-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4
The NM_006586.5(CNPY3):c.362G>A(p.Arg121Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CNPY3
NM_006586.5 missense
NM_006586.5 missense
Scores
8
4
Clinical Significance
Conservation
PhyloP100: 8.95
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, phyloP100way_vertebrate [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.35841575).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNPY3 | NM_006586.5 | c.362G>A | p.Arg121Gln | missense_variant | 3/6 | ENST00000372836.5 | |
CNPY3-GNMT | NR_134890.2 | n.329G>A | non_coding_transcript_exon_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNPY3 | ENST00000372836.5 | c.362G>A | p.Arg121Gln | missense_variant | 3/6 | 1 | NM_006586.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251430Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135890
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456776Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 724386
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 60 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics | Feb 14, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MutationTaster
Benign
D;D
Sift4G
Pathogenic
D
Vest4
MVP
ClinPred
D
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at