Variant 15-73591997-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_012428.4(NPTN):c.580A>C(p.Thr194Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000932 in 1,613,562 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

NPTN
NM_012428.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

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]

NPTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, NPTN

BP4

Computational evidence support a benign effect (MetaRNN=0.064043194).

BS2

High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPTN	NM_012428.4 linkuse as main transcript	c.580A>C	p.Thr194Pro	missense_variant	3/9	ENST00000345330.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPTN	ENST00000345330.9 linkuse as main transcript	c.580A>C	p.Thr194Pro	missense_variant	3/9	1	NM_012428.4	P4	Q9Y639-2

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000770

AC:

193

AN:

250772

Hom.:

AF XY:

0.000841

AC XY:

114

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.000833

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000961

AC:

1404

AN:

1461346

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

687

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000894

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152216

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.000544

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000799

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000831

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 submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.580A>C (p.T194P) alteration is located in exon 3 (coding exon 3) of the NPTN gene. This alteration results from a A to C substitution at nucleotide position 580, causing the threonine (T) at amino acid position 194 to be replaced by a proline (P). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.;.;.;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.064

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.032

D;T;T;D;T

Sift4G

Benign

0.17

T;T;T;T;.

Polyphen

1.0

D;.;D;D;.

Vest4

0.49

MVP

0.64

MPC

2.2

ClinPred

0.084

GERP RS

6.1

Varity_R

0.56

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over