17-41973576-ACTG-CCTA

Position:

• chr17-41973576-ACTG-CCTA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033133.5(CNP):​c.918_921delinsCCTA​(p.Gln306His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNP NM_033133.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNP	NM_033133.5	c.918_921delinsCCTA	p.Gln306His	missense_variant	4/4	ENST00000393892.8
CNP	NM_001330216.2	c.858_861delinsCCTA	p.Gln286His	missense_variant	4/4
CNP	XM_011524340.3	c.858_861delinsCCTA	p.Gln286His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8	c.918_921delinsCCTA	p.Gln306His	missense_variant	4/4	1	NM_033133.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukodystrophy, hypomyelinating, 20 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Neuberg Centre For Genomic Medicine, NCGM

-

The missense variant c.918_921delACTGinsCCTA in CNP (NM_033133.5) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.918_921delACTGinsCCTA variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. For these reasons, this variant has been classified as Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40125594;