dbSNP rs267599518: NXPE3:p.Pro96Ala (chr3-101801427-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145037.4(NXPE3):c.286C>G(p.Pro96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P96S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

NXPE3
NM_145037.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

Publications

0 publications found

Variant links:

Genes affected

NXPE3 (HGNC:28238): (neurexophilin and PC-esterase domain family member 3) This gene encodes a member of the neurexophilin family of neuropeptide-like glycoproteins. The encoded protein contains a variable N-terminal domain, a highly conserved neurexophilin and PC-esterase (NXPE) central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein binds alpha neurexins, a group of presynaptic transmembrane receptors that promote adhesion between dendrites and axons. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

NXPE3 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06032294).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145037.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NXPE3	NM_145037.4	MANE Select	c.286C>G	p.Pro96Ala	missense	Exon 5 of 8	NP_659474.1	Q969Y0
NXPE3	NM_001134456.2		c.286C>G	p.Pro96Ala	missense	Exon 5 of 8	NP_001127928.1	Q969Y0
NXPE3	NM_001348990.2		c.286C>G	p.Pro96Ala	missense	Exon 5 of 8	NP_001335919.1	Q969Y0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NXPE3	ENST00000273347.10	TSL:1 MANE Select	c.286C>G	p.Pro96Ala	missense	Exon 5 of 8	ENSP00000273347.5	Q969Y0
NXPE3	ENST00000477909.5	TSL:1	c.286C>G	p.Pro96Ala	missense	Exon 4 of 7	ENSP00000418369.1	Q969Y0
NXPE3	ENST00000474165.6	TSL:5	c.286C>G	p.Pro96Ala	missense	Exon 6 of 9	ENSP00000419667.2	C9K0A9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41442

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.064

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.031

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.70

M_CAP

Benign

0.0030

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

0.80

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.93

REVEL

Benign

0.050

Sift

Benign

0.30

Sift4G

Benign

0.48

Polyphen

0.0070

Vest4

0.066

MutPred

0.45

Loss of loop (P = 0.0203)

MVP

0.13

ClinPred

0.11

GERP RS

5.7

Varity_R

0.038

gMVP

0.42

Mutation Taster

=98/2

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over