17-80471755-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2

The NM_002522.4(NPTX1):​c.1054G>A​(p.Val352Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,612,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NPTX1
NM_002522.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 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
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPTX1NM_002522.4 linkc.1054G>A p.Val352Met missense_variant Exon 4 of 5 ENST00000306773.5 NP_002513.2 Q15818

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPTX1ENST00000306773.5 linkc.1054G>A p.Val352Met missense_variant Exon 4 of 5 1 NM_002522.4 ENSP00000307549.4 Q15818
NPTX1ENST00000571100.2 linkc.340G>A p.Val114Met missense_variant Exon 3 of 4 4 ENSP00000511957.1 A0A8Q3WL24
NPTX1ENST00000535681.1 linkn.1656G>A non_coding_transcript_exon_variant Exon 2 of 4 2
NPTX1ENST00000695485.1 linkn.477G>A non_coding_transcript_exon_variant Exon 3 of 4

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152258
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000401
AC:
10
AN:
249302
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135078
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000623
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1460498
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
39
AN XY:
726592
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000576
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152258
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Sep 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1054G>A (p.V352M) alteration is located in exon 4 (coding exon 4) of the NPTX1 gene. This alteration results from a G to A substitution at nucleotide position 1054, causing the valine (V) at amino acid position 352 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
0.12
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.050
D
MetaRNN
Uncertain
0.56
D
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.28
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.49
MVP
0.84
MPC
1.8
ClinPred
0.49
T
GERP RS
5.0
Varity_R
0.56

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: rs377120879; hg19: chr17-78445555; COSMIC: COSV60776401; COSMIC: COSV60776401; API