7-98617688-C-T

Variant summary

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

The NM_002523.3(NPTX2):​c.227C>T​(p.Thr76Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,458,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

NPTX2
NM_002523.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60
Variant links:
Genes affected
NPTX2 (HGNC:7953): (neuronal pentraxin 2) This gene encodes a member of the family of neuronal petraxins, synaptic proteins that are related to C-reactive protein. This protein is involved in excitatory synapse formation. It also plays a role in clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors at established synapses, resulting in non-apoptotic cell death of dopaminergic nerve cells. Up-regulation of this gene in Parkinson disease (PD) tissues suggests that the protein may be involved in the pathology of PD. [provided by RefSeq, Feb 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
NPTX2NM_002523.3 linkc.227C>T p.Thr76Met missense_variant Exon 1 of 5 ENST00000265634.4 NP_002514.1 P47972

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPTX2ENST00000265634.4 linkc.227C>T p.Thr76Met missense_variant Exon 1 of 5 1 NM_002523.3 ENSP00000265634.3 P47972

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
AF:
0.00000536
AC:
7
AN:
1306340
Hom.:
0
Cov.:
31
AF XY:
0.00000623
AC XY:
4
AN XY:
642386
show subpopulations
Gnomad4 AFR exome
AF:
0.000232
Gnomad4 AMR exome
AF:
0.0000442
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152092
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000718

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.227C>T (p.T76M) alteration is located in exon 1 (coding exon 1) of the NPTX2 gene. This alteration results from a C to T substitution at nucleotide position 227, causing the threonine (T) at amino acid position 76 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.34
D
MetaRNN
Uncertain
0.54
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Pathogenic
0.96
D
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.099
Sift
Benign
0.033
D
Sift4G
Benign
0.074
T
Polyphen
1.0
D
Vest4
0.53
MutPred
0.24
Gain of catalytic residue at T76 (P = 0.0012);
MVP
0.26
MPC
0.95
ClinPred
0.99
D
GERP RS
3.6
Varity_R
0.33
gMVP
0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs932379106; hg19: chr7-98247000; COSMIC: COSV99674713; COSMIC: COSV99674713; API