Variant 11-114522967-T-C 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_001395504.1(NXPE1):c.1020A>G(p.Ile340Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,446 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NXPE1
NM_001395504.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.811

Variant links:

Genes affected

NXPE1 (HGNC:28527): (neurexophilin and PC-esterase domain family member 1) Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NXPE1 links:

NXPE1 (HGNC:):

NXPE1 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 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=0.09725362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPE1	NM_001395504.1 linkuse as main transcript	c.1020A>G	p.Ile340Met	missense_variant	8/9	ENST00000534921.3	NP_001382433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NXPE1	ENST00000534921.3 linkuse as main transcript	c.1020A>G	p.Ile340Met	missense_variant	8/9	3	NM_001395504.1	ENSP00000439503.2	Q8N323-1
NXPE1	ENST00000251921.6 linkuse as main transcript	c.594A>G	p.Ile198Met	missense_variant	5/6	1		ENSP00000251921.2	Q8N323-2
NXPE1	ENST00000536271.5 linkuse as main transcript	n.1412A>G		non_coding_transcript_exon_variant	3/4	1
NXPE1	ENST00000696071.1 linkuse as main transcript	c.1020A>G	p.Ile340Met	missense_variant	7/8			ENSP00000512373.1	Q8N323-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461446

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

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

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

Feb 21, 2024

The c.594A>G (p.I198M) alteration is located in exon 5 (coding exon 3) of the NXPE1 gene. This alteration results from a A to G substitution at nucleotide position 594, causing the isoleucine (I) at amino acid position 198 to be replaced by a methionine (M). 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

0.078

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.54

DANN

Benign

0.57

DEOGEN2

Benign

0.010

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.24

.;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.097

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.96

L;.;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

.;N;N

REVEL

Benign

0.015

Sift

Benign

0.36

.;T;T

Sift4G

Benign

0.43

.;T;T

Polyphen

0.010

B;.;B

Vest4

0.18, 0.18

MutPred

0.58

Loss of helix (P = 0.079);.;Loss of helix (P = 0.079);

MVP

0.085

MPC

0.025

ClinPred

0.13

GERP RS

-2.7

Varity_R

0.059

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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