Variant chr11-114571001-A-C 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_001077639.2(NXPE4):c.1572T>G(p.Asn524Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NXPE4
NM_001077639.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.36

Variant links:

Genes affected

NXPE4 (HGNC:23117): (neurexophilin and PC-esterase domain family member 4) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

NXPE4 links:

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:

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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=0.057982624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPE4	NM_001077639.2 linkuse as main transcript	c.1572T>G	p.Asn524Lys	missense_variant	6/6	ENST00000375478.4	NP_001071107.1	Q6UWF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXPE4	ENST00000375478.4 linkuse as main transcript	c.1572T>G	p.Asn524Lys	missense_variant	6/6	1	NM_001077639.2	ENSP00000364627.3		Q6UWF7-1
NXPE4	ENST00000424261.6 linkuse as main transcript	c.720T>G	p.Asn240Lys	missense_variant	6/6	1		ENSP00000401503.2		Q6UWF7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

248950

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460952

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726772

show subpopulations

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:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 06, 2023

The c.1572T>G (p.N524K) alteration is located in exon 6 (coding exon 5) of the NXPE4 gene. This alteration results from a T to G substitution at nucleotide position 1572, causing the asparagine (N) at amino acid position 524 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.8

DANN

Benign

0.90

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.029

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.035

Sift

Benign

0.22

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.037

.;B

Vest4

0.096

MutPred

0.35

.;Gain of methylation at N524 (P = 0.0056);

MVP

0.014

MPC

0.12

ClinPred

0.077

GERP RS

-7.1

Varity_R

0.11

gMVP

0.26

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