dbSNP rs1340574300: NXPH4:p.Ala45Asp (chr12-57224954-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007224.4(NXPH4):c.134C>A(p.Ala45Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. A45V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NXPH4
NM_007224.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

Publications

1 publications found

Variant links:

Genes affected

NXPH4 (HGNC:8078): (neurexophilin 4) Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

NXPH4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08636311).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007224.4. 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
	NXPH4	NM_007224.4	MANE Select	c.134C>A	p.Ala45Asp	missense	Exon 2 of 2	NP_009155.1	O95158

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NXPH4	ENST00000349394.6	TSL:1 MANE Select	c.134C>A	p.Ala45Asp	missense	Exon 2 of 2	ENSP00000333593.6	O95158
NXPH4	ENST00000555154.1	TSL:3	n.185C>A		non_coding_transcript_exon	Exon 2 of 2
NXPH4	ENST00000556415.1	TSL:2	n.*261C>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000452288.1	G3V5C5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1253006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

612110

African (AFR)

AF:

0.00

AC:

AN:

25090

American (AMR)

AF:

0.00

AC:

AN:

19182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18804

East Asian (EAS)

AF:

0.00

AC:

AN:

29822

South Asian (SAS)

AF:

0.00

AC:

AN:

58750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4450

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1008672

Other (OTH)

AF:

0.00

AC:

AN:

51470

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.40

M_CAP

Benign

0.014

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.068

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.79

REVEL

Benign

0.034

Sift

Uncertain

0.0070

Sift4G

Benign

0.093

Polyphen

0.013

Vest4

0.22

MutPred

0.43

Gain of catalytic residue at A43 (P = 0.0055)

MVP

0.12

MPC

1.3

ClinPred

0.080

GERP RS

2.8

Varity_R

0.11

gMVP

0.48

Mutation Taster

=93/7

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