15-73570333-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012428.4(NPTN):​c.931C>T​(p.Pro311Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,010 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: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NPTN
NM_012428.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.48
Variant links:
Genes affected
NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPTNNM_012428.4 linkuse as main transcriptc.931C>T p.Pro311Ser missense_variant 6/9 ENST00000345330.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPTNENST00000345330.9 linkuse as main transcriptc.931C>T p.Pro311Ser missense_variant 6/91 NM_012428.4 P4Q9Y639-2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000800
AC:
2
AN:
250146
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135282
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461822
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000578
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 13, 2024The c.931C>T (p.P311S) alteration is located in exon 6 (coding exon 6) of the NPTN gene. This alteration results from a C to T substitution at nucleotide position 931, causing the proline (P) at amino acid position 311 to be replaced by a serine (S). 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
Pathogenic
0.71
BayesDel_addAF
Benign
0.0098
T
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T;.;T;.;.;T
Eigen
Uncertain
0.58
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.93
D;D;T;D;D;D
M_CAP
Benign
0.065
D
MetaRNN
Uncertain
0.71
D;D;D;D;D;D
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
-0.49
N;.;.;.;N;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-6.3
D;D;D;D;D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0070
D;D;D;D;D;D
Sift4G
Uncertain
0.050
T;D;.;D;T;.
Polyphen
1.0
D;.;.;D;D;.
Vest4
0.66
MVP
0.56
MPC
1.7
ClinPred
0.85
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.66
gMVP
0.89

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: rs371300963; hg19: chr15-73862674; API