Variant 7-8435763-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_152745.3(NXPH1):c.50A>G(p.Tyr17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NXPH1
NM_152745.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Variant links:

Genes affected

NXPH1 (HGNC:20693): (neurexophilin 1) This gene is a member of the neurexophilin family and encodes a secreted protein with a variable N-terminal domain, a highly conserved, N-glycosylated central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein forms a very tight complex with alpha neurexins, a group of proteins that promote adhesion between dendrites and axons. [provided by RefSeq, Jul 2008]

NXPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPH1	NM_152745.3 linkuse as main transcript	c.50A>G	p.Tyr17Cys	missense_variant	2/3	ENST00000405863.6	NP_689958.1	P58417Q3LID8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NXPH1	ENST00000405863.6 linkuse as main transcript	c.50A>G	p.Tyr17Cys	missense_variant	2/3	1	NM_152745.3	ENSP00000384551.1	P58417
NXPH1	ENST00000429542.1 linkuse as main transcript	c.50A>G	p.Tyr17Cys	missense_variant	1/2	1		ENSP00000408216.1	C9JPD0
NXPH1	ENST00000438764.1 linkuse as main transcript	c.50A>G	p.Tyr17Cys	missense_variant	2/3	4		ENSP00000404689.1	C9JE46

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249240

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135216

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727120

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

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

Dec 04, 2024

The c.50A>G (p.Y17C) alteration is located in exon 2 (coding exon 1) of the NXPH1 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the tyrosine (Y) at amino acid position 17 to be replaced by a cysteine (C). 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

0.067

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.025

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.0097

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

L;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.17

T;T;T

Polyphen

0.044

B;.;.

Vest4

0.48

MutPred

0.75

Gain of catalytic residue at L18 (P = 0.0096);Gain of catalytic residue at L18 (P = 0.0096);Gain of catalytic residue at L18 (P = 0.0096);

MVP

0.068

MPC

0.34

ClinPred

0.51

GERP RS

4.4

Varity_R

0.23

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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