Variant chr6-42935615-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006586.5(CNPY3):c.317G>T(p.Arg106Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CNPY3
NM_006586.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.95

Variant links:

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 links:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPY3	NM_006586.5 linkuse as main transcript	c.317G>T	p.Arg106Met	missense_variant	3/6	ENST00000372836.5	NP_006577.2	Q9BT09-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNPY3	ENST00000372836.5 linkuse as main transcript	c.317G>T	p.Arg106Met	missense_variant	3/6	1	NM_006586.5	ENSP00000361926.4		Q9BT09-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460008

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CNPY3-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 06, 2024

The CNPY3 c.317G>T variant is predicted to result in the amino acid substitution p.Arg106Met. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.38

.;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

T;D

M_CAP

Benign

0.073

MetaRNN

Pathogenic

0.75

D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.4

.;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.71

MutPred

0.49

Gain of ubiquitination at K105 (P = 0.0577);Gain of ubiquitination at K105 (P = 0.0577);

MVP

0.56

MPC

0.67

ClinPred

1.0

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over