rs1305796791

Variant names:

• chr7-98617521-C-A
• NM_002523.3:c.60C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-98617521-C-A
• chr7-98617521-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002523.3(NPTX2):​c.60C>A​(p.Ser20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,251,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: NPTX2 NM_002523.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05389604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPTX2	NM_002523.3	c.60C>A	p.Ser20Arg	missense_variant	Exon 1 of 5	ENST00000265634.4	NP_002514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTX2	ENST00000265634.4	c.60C>A	p.Ser20Arg	missense_variant	Exon 1 of 5	1	NM_002523.3	ENSP00000265634.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1251138 Hom.: 0 Cov.: 30 AF XY: 0.00000163 AC XY: 1 AN XY: 612002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000196

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.030	N
REVEL	Benign	0.043
Sift	Benign	0.76	T
Sift4G	Benign	0.53	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.18		Loss of glycosylation at S20 (P = 0.0112);
MVP		0.23
MPC		0.39
ClinPred		0.22	T
GERP RS		2.3
Varity_R		0.089
gMVP		0.43

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: chr7-98246833;