Genetic Variant NXPH1:p.Asn93Lys (chr7-8751232-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM1BS2

The NM_152745.3(NXPH1):c.279C>G(p.Asn93Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

NXPH1
NM_152745.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity NXPH1_HUMAN

BS2

High AC in GnomAdExome4 at 49 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152745.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPH1	NM_152745.3	MANE Select	c.279C>G	p.Asn93Lys	missense	Exon 3 of 3	NP_689958.1	P58417

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NXPH1	ENST00000405863.6	TSL:1 MANE Select	c.279C>G	p.Asn93Lys	missense	Exon 3 of 3	ENSP00000384551.1	P58417
NXPH1	ENST00000429542.1	TSL:1	c.279C>G	p.Asn93Lys	missense	Exon 2 of 2	ENSP00000408216.1	C9JPD0
NXPH1	ENST00000602349.2	TSL:6	c.225C>G	p.Asn75Lys	missense	Exon 1 of 1	ENSP00000473269.2	R4GMM9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248744

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461536

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1111788

Other (OTH)

AF:

0.0000166

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.52

MetaSVM

Uncertain

-0.094

MutationAssessor

Uncertain

2.3

PhyloP100

3.1

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.28

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.57

MutPred

0.55

Gain of ubiquitination at N93 (P = 0.0117)

MVP

0.34

MPC

0.95

ClinPred

0.97

GERP RS

5.2

PromoterAI

0.015

Neutral

(source)

Varity_R

0.66

gMVP

0.73

Mutation Taster

=20/80

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over