Variant 11-114705960-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182495.6(NXPE2):c.1108C>A(p.His370Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000334 in 1,498,886 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 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NXPE2
NM_182495.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0440

Variant links:

Genes affected

NXPE2 (HGNC:26331): (neurexophilin and PC-esterase domain family member 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NXPE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036530197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPE2	NM_182495.6 linkuse as main transcript	c.1108C>A	p.His370Asn	missense_variant	5/6	ENST00000389586.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPE2	ENST00000389586.6 linkuse as main transcript	c.1108C>A	p.His370Asn	missense_variant	5/6	5	NM_182495.6	P1	Q96DL1-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000868

AC:

AN:

115144

Hom.:

AF XY:

0.00

AC XY:

AN XY:

61502

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000702

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1346728

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

663310

show subpopulations

Gnomad4 AFR exome

AF:

0.000517

Gnomad4 AMR exome

AF:

0.000185

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:

9.47e-7

Gnomad4 OTH exome

AF:

0.0000718

GnomAD4 genome

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000215

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

Nov 12, 2021

The c.1108C>A (p.H370N) alteration is located in exon 5 (coding exon 5) of the NXPE2 gene. This alteration results from a C to A substitution at nucleotide position 1108, causing the histidine (H) at amino acid position 370 to be replaced by an asparagine (N). 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

0.28

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.043

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.26

M_CAP

Benign

0.0067

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.49

REVEL

Benign

0.052

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

0.0020

Vest4

0.23

MVP

0.030

MPC

0.011

ClinPred

0.18

GERP RS

2.2

Varity_R

0.15

gMVP

0.47

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