Variant 11-114523035-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_001395504.1(NXPE1):c.952G>A(p.Gly318Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,613,720 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 3 hom. )

Consequence

NXPE1
NM_001395504.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01020059).

BP6

Variant 11-114523035-C-T is Benign according to our data. Variant chr11-114523035-C-T is described in ClinVar as [Benign]. Clinvar id is 720449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPE1	NM_001395504.1 linkuse as main transcript	c.952G>A	p.Gly318Ser	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.952G>A	p.Gly318Ser	missense_variant	8/9	3	NM_001395504.1	ENSP00000439503.2	Q8N323-1
NXPE1	ENST00000251921.6 linkuse as main transcript	c.526G>A	p.Gly176Ser	missense_variant	5/6	1		ENSP00000251921.2	Q8N323-2
NXPE1	ENST00000536271.5 linkuse as main transcript	n.1344G>A		non_coding_transcript_exon_variant	3/4	1
NXPE1	ENST00000696071.1 linkuse as main transcript	c.952G>A	p.Gly318Ser	missense_variant	7/8			ENSP00000512373.1	Q8N323-1

Frequencies

GnomAD3 genomes

AF:

0.00335

AC:

509

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

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:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000900

AC:

226

AN:

251188

Hom.:

AF XY:

0.000656

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000374

AC:

546

AN:

1461512

Hom.:

Cov.:

AF XY:

0.000344

AC XY:

250

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000738

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:

0.0000612

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.00334

AC:

508

AN:

152208

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

237

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.00358

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00103

AC:

125

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.;T

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.62

.;T;T

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Pathogenic

3.2

M;.;M

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.8

.;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0030

.;D;D

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

1.0

D;.;D

Vest4

0.82, 0.82

MVP

0.45

MPC

0.15

ClinPred

0.091

GERP RS

4.4

Varity_R

0.58

gMVP

0.54

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