Variant 18-72865236-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138966.5(NETO1):c.34G>A(p.Ala12Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00379 in 1,611,914 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 31 hom. )

Consequence

NETO1
NM_138966.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.47

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008216709).

BP6

Variant 18-72865236-C-T is Benign according to our data. Variant chr18-72865236-C-T is described in ClinVar as [Benign]. Clinvar id is 788659.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NETO1	NM_138966.5 linkuse as main transcript	c.34G>A	p.Ala12Thr	missense_variant	2/11	ENST00000327305.11	NP_620416.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NETO1	ENST00000327305.11 linkuse as main transcript	c.34G>A	p.Ala12Thr	missense_variant	2/11	1	NM_138966.5	ENSP00000313088	P1	Q8TDF5-3

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

441

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00373

AC:

930

AN:

249018

Hom.:

AF XY:

0.00370

AC XY:

498

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.000752

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.00547

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00388

AC:

5668

AN:

1459726

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

2741

AN XY:

726144

show subpopulations

Gnomad4 AFR exome

AF:

0.000479

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0133

Gnomad4 NFE exome

AF:

0.00431

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00290

AC:

441

AN:

152188

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00201

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00422

AC:

512

Asia WGS

AF:

0.000289

AC:

AN:

3472

EpiCase

AF:

0.00278

EpiControl

AF:

0.00327

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

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.082

T;T;.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

.;T;T;T

MetaRNN

Benign

0.0082

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.070

.;N;N;.

REVEL

Benign

0.095

Sift

Benign

0.63

.;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0020

B;B;B;.

Vest4

0.43

MVP

0.35

MPC

0.53

ClinPred

0.014

GERP RS

5.8

Varity_R

0.11

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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