Genetic Variant NXPH1:p.Cys21Ser (chr7-8751014-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_152745.3(NXPH1):c.61T>A(p.Cys21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NXPH1
NM_152745.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 21 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.61T>A	p.Cys21Ser	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.61T>A	p.Cys21Ser	missense	Exon 3 of 3	ENSP00000384551.1	P58417
NXPH1	ENST00000429542.1	TSL:1	c.61T>A	p.Cys21Ser	missense	Exon 2 of 2	ENSP00000408216.1	C9JPD0
NXPH1	ENST00000602349.2	TSL:6	c.7T>A	p.Cys3Ser	missense	Exon 1 of 1	ENSP00000473269.2	R4GMM9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000321

AC:

AN:

248884

AF XY:

0.0000444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461184

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.000128

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111466

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000497

AC:

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

Benign

0.086

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.20

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.021

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.75

M_CAP

Benign

0.0018

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

3.2

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.1

REVEL

Benign

0.12

Sift

Benign

0.12

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.17

MutPred

0.93

Gain of disorder (P = 0.0058)

MVP

0.043

MPC

0.31

ClinPred

0.031

GERP RS

4.7

PromoterAI

-0.042

Neutral

(source)

Varity_R

0.19

gMVP

0.32

Mutation Taster

=82/18

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over