NM_002522.4:c.428G>T

Variant names:

• chr17-80476019-C-A
• NM_002522.4:c.428G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_002522.4(NPTX1):​c.428G>T​(p.Arg143Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NPTX1 NM_002522.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.51

Genes affected

NPTX1 (HGNC:7952): (neuronal pentraxin 1) NPTX1 is a member of the neuronal pentraxin gene family. Neuronal pentraxin 1 is similar to the rat NP1 gene which encodes a binding protein for the snake venom toxin taipoxin. Human NPTX1 mRNA is exclusively localized to the nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75
• PP5: Variant 17-80476019-C-A is Pathogenic according to our data. Variant chr17-80476019-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 1806389.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPTX1	NM_002522.4	c.428G>T	p.Arg143Leu	missense_variant	Exon 1 of 5	ENST00000306773.5	NP_002513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTX1	ENST00000306773.5	c.428G>T	p.Arg143Leu	missense_variant	Exon 1 of 5	1	NM_002522.4	ENSP00000307549.4
NPTX1	ENST00000575212.1	n.234-301G>T		intron_variant	Intron 1 of 2	4
NPTX1	ENST00000571100.2	c.-571G>T		upstream_gene_variant		4		ENSP00000511957.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spinocerebellar ataxia 50 Pathogenic:1

Dec 20, 2022

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	0.0047	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.34		Loss of helix (P = 0.0304);
MVP		0.53
MPC		1.9
ClinPred		1.0	D
GERP RS		2.3
Varity_R		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78449819;