Variant chr18-72749041-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138966.5(NETO1):c.1589C>A(p.Thr530Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NETO1
NM_138966.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NETO1	NM_138966.5 link	c.1589C>A	p.Thr530Lys	missense_variant	10/11	ENST00000327305.11	NP_620416.2	Q8TDF5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NETO1	ENST00000327305.11 link	c.1589C>A	p.Thr530Lys	missense_variant	10/11	1	NM_138966.5	ENSP00000313088.6	Q8TDF5-3
NETO1	ENST00000583169.5 link	c.1589C>A	p.Thr530Lys	missense_variant	10/11	1		ENSP00000464312.1	Q8TDF5-3
NETO1	ENST00000582281.1 link	c.-5C>A		upstream_gene_variant		5		ENSP00000462993.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725820

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.1589C>A (p.T530K) alteration is located in exon 10 (coding exon 10) of the NETO1 gene. This alteration results from a C to A substitution at nucleotide position 1589, causing the threonine (T) at amino acid position 530 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.58

.;N

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.75

MutPred

0.27

Gain of ubiquitination at T530 (P = 0.0054);Gain of ubiquitination at T530 (P = 0.0054);

MVP

0.49

MPC

1.6

ClinPred

0.89

GERP RS

5.6

Varity_R

0.44

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over