17-80471829-T-C

Variant names:

• chr17-80471829-T-C
• NM_002522.4:c.980A>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3 PP5

The NM_002522.4(NPTX1):​c.980A>G​(p.Glu327Gly) 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: 34)
• Consequence: NPTX1 NM_002522.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.20

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a domain Pentraxin (PTX) (size 202) in uniprot entity NPTX1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_002522.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807
• PP5: Variant 17-80471829-T-C is Pathogenic according to our data. Variant chr17-80471829-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1806388.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.980A>G	p.Glu327Gly	missense_variant	Exon 4 of 5	ENST00000306773.5	NP_002513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTX1	ENST00000306773.5	c.980A>G	p.Glu327Gly	missense_variant	Exon 4 of 5	1	NM_002522.4	ENSP00000307549.4
NPTX1	ENST00000571100.2	c.266A>G	p.Glu89Gly	missense_variant	Exon 3 of 4	4		ENSP00000511957.1
NPTX1	ENST00000535681.1	n.1582A>G		non_coding_transcript_exon_variant	Exon 2 of 4	2
NPTX1	ENST00000695485.1	n.403A>G		non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

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	0.61
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.32
Sift	Benign	0.039	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.62		Loss of catalytic residue at E327 (P = 0.0672);
MVP		0.75
MPC		1.4
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78445629;