Variant 15-24676003-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018958.3(NPAP1):c.136C>T(p.Pro46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 1,600,666 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 47 hom. )

Consequence

NPAP1
NM_018958.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0330

Variant links:

Genes affected

NPAP1 (HGNC:1190): (nuclear pore associated protein 1) This intronless retrogene is located in the Prader-Willi syndrome region on chromosome 15. This gene exhibits tissue-specific imprinting. Expression in adult testis and brain is biallelic, while expression in fetal brain is monoallelic and only from the paternal chromosome. The encoded protein is associated with the nuclear pore complex. [provided by RefSeq, Mar 2021]

NPAP1 links:

ENSG00000286110 (HGNC:):

ENSG00000286110 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058502555).

BP6

Variant 15-24676003-C-T is Benign according to our data. Variant chr15-24676003-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 789222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAP1	NM_018958.3 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/1	ENST00000329468.5	NP_061831.2	Q9NZP6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAP1	ENST00000329468.5 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/1	6	NM_018958.3	ENSP00000333735.3		Q9NZP6

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

737

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00869

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00398

AC:

899

AN:

226022

Hom.:

AF XY:

0.00390

AC XY:

487

AN XY:

124974

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.000552

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000409

Gnomad FIN exome

AF:

0.00260

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00518

GnomAD4 exome

AF:

0.00746

AC:

10800

AN:

1448366

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

5110

AN XY:

720572

show subpopulations

Gnomad4 AFR exome

AF:

0.000684

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00114

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000599

Gnomad4 FIN exome

AF:

0.00227

Gnomad4 NFE exome

AF:

0.00906

Gnomad4 OTH exome

AF:

0.00767

GnomAD4 genome

AF:

0.00484

AC:

737

AN:

152300

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00869

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00655

Hom.:

Bravo

AF:

0.00453

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00186

AC:

ESP6500EA

AF:

0.00705

AC:

ExAC

AF:

0.00374

AC:

449

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	NPAP1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.37

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.040

Sift

Benign

0.038

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.16

MVP

0.072

MPC

0.32

ClinPred

0.027

GERP RS

1.3

Varity_R

0.086

gMVP

0.28

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.

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