NM_002523.3:c.58A>C

Variant names:

• chr7-98617519-A-C
• rs995333515
• NM_002523.3:c.58A>C
• NPTX2 p.Ser20Arg

Variant summary

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

The NM_002523.3(NPTX2):​c.58A>C​(p.Ser20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPTX2 NM_002523.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 0 publications found

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]

ENSG00000306503 (HGNC:):

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=0.08201635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002523.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTX2	NM_002523.3	MANE Select	c.58A>C	p.Ser20Arg	missense	Exon 1 of 5	NP_002514.1	P47972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTX2	ENST00000265634.4	TSL:1 MANE Select	c.58A>C	p.Ser20Arg	missense	Exon 1 of 5	ENSP00000265634.3	P47972
	NPTX2	ENST00000903470.1		c.58A>C	p.Ser20Arg	missense	Exon 1 of 5	ENSP00000573529.1
	ENSG00000306503	ENST00000819136.1		n.179+1695T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151452 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1242726 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 607416

African (AFR) AF: 0.00 AC: 0 AN: 24820

American (AMR) AF: 0.00 AC: 0 AN: 17576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19804

East Asian (EAS) AF: 0.00 AC: 0 AN: 26454

South Asian (SAS) AF: 0.00 AC: 0 AN: 60110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1008598

Other (OTH) AF: 0.00 AC: 0 AN: 50722

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151452 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73956

African (AFR) AF: 0.0000242 AC: 1 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67810

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.078
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.030	N
REVEL	Benign	0.035
Sift	Benign	0.76	T
Sift4G	Benign	0.53	T
PromoterAI		0.0092	Neutral
Varity_R		0.050
gMVP		0.43
Mutation Taster		=95/5	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs995333515;

hg19: chr7-98246831;