Variant 17-41968123-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP5

The NM_033133.5(CNP):c.59A>C(p.Lys20Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K20R) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CNP
NM_033133.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.56

Variant links:

Genes affected

CNP (HGNC:2158): (2',3'-cyclic nucleotide 3' phosphodiesterase) Predicted to enable 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity. Involved in substantia nigra development. Located in several cellular components, including extracellular space; microtubule; and plasma membrane. Implicated in hypomyelinating leukodystrophy 20; multiple sclerosis; and schizophrenia. Biomarker of alcoholic liver cirrhosis; multiple sclerosis; and restless legs syndrome. [provided by Alliance of Genome Resources, Apr 2022]

CNP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-41968123-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 834077.Status of the report is no_assertion_criteria_provided, 0 stars.

PP5

Variant 17-41968123-A-C is Pathogenic according to our data. Variant chr17-41968123-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 693983.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNP	NM_033133.5 linkuse as main transcript	c.59A>C	p.Lys20Thr	missense_variant	2/4	ENST00000393892.8
CNP	NM_001330216.2 linkuse as main transcript	c.-2A>C		5_prime_UTR_variant	2/4
CNP	XM_011524340.3 linkuse as main transcript	c.-2A>C		5_prime_UTR_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8 linkuse as main transcript	c.59A>C	p.Lys20Thr	missense_variant	2/4	1	NM_033133.5	P3	P09543-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myopia 2, autosomal dominant

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department of Animal Sciences, Quaid-i-Azam University

Oct 14, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Uncertain

0.011

Sift4G

Benign

0.065

Polyphen

0.98

Vest4

0.46

MutPred

0.26

Loss of methylation at K20 (P = 0.0184);

MVP

0.72

MPC

2.6

ClinPred

0.93

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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