Variant 18-72750143-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138966.5(NETO1):c.1460C>G(p.Ala487Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00323 in 1,613,800 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.018 ( 83 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 72 hom. )

Consequence

NETO1
NM_138966.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.15

Variant links:

Genes affected

NETO1 (HGNC:13823): (neuropilin and tolloid like 1) This gene encodes a transmembrane protein containing two extracellular CUB domains followed by a low-density lipoprotein class A (LDLa) domain. This protein is thought to play a critical role in spatial learning and memory by regulating the function of synaptic N-methyl-D-aspartic acid receptor complexes in the hippocampus. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2017]

NETO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002880007).

BP6

Variant 18-72750143-G-C is Benign according to our data. Variant chr18-72750143-G-C is described in ClinVar as [Benign]. Clinvar id is 778776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NETO1	NM_138966.5 link	c.1460C>G	p.Ala487Gly	missense_variant	9/11	ENST00000327305.11	NP_620416.2	Q8TDF5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NETO1	ENST00000327305.11 link	c.1460C>G	p.Ala487Gly	missense_variant	9/11	1	NM_138966.5	ENSP00000313088.6		Q8TDF5-3
NETO1	ENST00000583169.5 link	c.1460C>G	p.Ala487Gly	missense_variant	9/11	1		ENSP00000464312.1		Q8TDF5-3

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2722

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00459

AC:

1153

AN:

250994

Hom.:

AF XY:

0.00342

AC XY:

464

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00170

AC:

2482

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1059

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0630

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.0179

AC:

2727

AN:

152242

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1314

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0632

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00263

Hom.:

Bravo

AF:

0.0196

ESP6500AA

AF:

0.0601

AC:

265

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00581

AC:

706

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.90

L;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.17

.;N

REVEL

Benign

0.13

Sift

Benign

0.14

.;T

Sift4G

Benign

0.099

T;T

Polyphen

0.61

P;P

Vest4

0.42

MVP

0.30

MPC

0.84

ClinPred

0.021

GERP RS

4.9

Varity_R

0.14

gMVP

0.41

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