Variant 15-24676197-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018958.3(NPAP1):c.330C>A(p.His110Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPAP1
NM_018958.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.626

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14695552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAP1	NM_018958.3 linkuse as main transcript	c.330C>A	p.His110Gln	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.330C>A	p.His110Gln	missense_variant	1/1	6	NM_018958.3	ENSP00000333735.3		Q9NZP6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1401826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691982

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:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

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:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Aug 14, 2023

The c.330C>A (p.H110Q) alteration is located in exon 1 (coding exon 1) of the NPAP1 gene. This alteration results from a C to A substitution at nucleotide position 330, causing the histidine (H) at amino acid position 110 to be replaced by a glutamine (Q). 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

0.33

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.7

DANN

Benign

0.68

DEOGEN2

Benign

0.010

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.26

M_CAP

Benign

0.00086

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.0

REVEL

Benign

0.036

Sift

Benign

0.17

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.11

MutPred

0.23

Loss of methylation at R107 (P = 0.0471);

MVP

0.014

MPC

0.35

ClinPred

0.41

GERP RS

1.5

Varity_R

0.046

gMVP

0.12

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