rs782078035

Variant names:

• chr17-41973506-C-A
• rs782078035
• NM_033133.5:c.848C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41973506-C-A
• chr17-41973506-C-G
• chr17-41973506-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033133.5(CNP):​c.848C>A​(p.Thr283Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. T283M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNP NM_033133.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 20

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09696159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNP	NM_033133.5	c.848C>A	p.Thr283Lys	missense_variant	Exon 4 of 4	ENST00000393892.8	NP_149124.3
CNP	NM_001330216.2	c.788C>A	p.Thr263Lys	missense_variant	Exon 4 of 4		NP_001317145.1
CNP	XM_011524340.3	c.788C>A	p.Thr263Lys	missense_variant	Exon 4 of 4		XP_011522642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNP	ENST00000393892.8	c.848C>A	p.Thr283Lys	missense_variant	Exon 4 of 4	1	NM_033133.5	ENSP00000377470.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.82
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
PhyloP100		0.34
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.038
Sift	Benign	0.76	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.016	B;.
Vest4		0.10
MutPred		0.56		Gain of methylation at T283 (P = 0.0022);.;
MVP		0.39
MPC		0.36
ClinPred		0.44	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782078035; hg19: chr17-40125524;