Variant 7-8751352-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152745.3(NXPH1):c.399G>A(p.Leu133Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,613,904 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0088 ( 73 hom. )

Consequence

NXPH1
NM_152745.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.701

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-8751352-G-A is Benign according to our data. Variant chr7-8751352-G-A is described in ClinVar as [Benign]. Clinvar id is 779337.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.701 with no splicing effect.

BS2

High AC in GnomAd4 at 970 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPH1	NM_152745.3 link	c.399G>A	p.Leu133Leu	synonymous_variant	3/3	ENST00000405863.6	NP_689958.1	P58417Q3LID8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXPH1	ENST00000405863.6 link	c.399G>A	p.Leu133Leu	synonymous_variant	3/3	1	NM_152745.3	ENSP00000384551.1		P58417

Frequencies

GnomAD3 genomes

AF:

0.00638

AC:

971

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00592

AC:

1473

AN:

248686

Hom.:

AF XY:

0.00612

AC XY:

826

AN XY:

134902

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00604

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00663

GnomAD4 exome

AF:

0.00875

AC:

12792

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00860

AC XY:

6250

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00627

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

AF:

0.00637

AC:

970

AN:

152328

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00850

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00731

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00998

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.6

DANN

Benign

0.72

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

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