Genetic Variant NM_006586.5:c.68T>G (chr6-42929638-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006586.5(CNPY3):c.68T>G(p.Leu23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L23P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CNPY3
NM_006586.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found

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 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 links:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30422643).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CNPY3	NM_006586.5	MANE Select	c.68T>G	p.Leu23Arg	missense	Exon 1 of 6	NP_006577.2
CNPY3	NM_001318842.1		c.68T>G	p.Leu23Arg	missense	Exon 1 of 7	NP_001305771.1
CNPY3-GNMT	NM_001318857.2		c.68T>G	p.Leu23Arg	missense	Exon 1 of 5	NP_001305786.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNPY3	ENST00000372836.5	TSL:1 MANE Select	c.68T>G	p.Leu23Arg	missense	Exon 1 of 6	ENSP00000361926.4	Q9BT09-1
CNPY3	ENST00000893179.1		c.68T>G	p.Leu23Arg	missense	Exon 1 of 6	ENSP00000563238.1
CNPY3	ENST00000924680.1		c.68T>G	p.Leu23Arg	missense	Exon 1 of 7	ENSP00000594739.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1403630

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32004

American (AMR)

AF:

0.00

AC:

AN:

35966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25218

East Asian (EAS)

AF:

0.00

AC:

AN:

36336

South Asian (SAS)

AF:

0.00

AC:

AN:

79948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1082862

Other (OTH)

AF:

0.00

AC:

AN:

58236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.45

M_CAP

Benign

0.014

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

1.1

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.21

Sift

Uncertain

0.022

Sift4G

Uncertain

0.0030

Polyphen

0.24

Vest4

0.59

MutPred

0.45

Gain of solvent accessibility (P = 0.0171)

MVP

0.10

MPC

0.51

ClinPred

0.92

GERP RS

-0.40

PromoterAI

-0.0021

Neutral

(source)

Varity_R

0.39

gMVP

0.76

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over