18-72794155-C-T

Variant names:

• chr18-72794155-C-T
• NM_138966.5:c.601G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138966.5(NETO1):​c.601G>A​(p.Asp201Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NETO1 NM_138966.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NETO1	NM_138966.5	c.601G>A	p.Asp201Asn	missense_variant	Exon 6 of 11	ENST00000327305.11	NP_620416.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NETO1	ENST00000327305.11	c.601G>A	p.Asp201Asn	missense_variant	Exon 6 of 11	1	NM_138966.5	ENSP00000313088.6
NETO1	ENST00000583169.5	c.601G>A	p.Asp201Asn	missense_variant	Exon 6 of 11	1		ENSP00000464312.1
NETO1	ENST00000579730.2	n.303-10249G>A		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>A (p.D201N) alteration is located in exon 6 (coding exon 6) of the NETO1 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the aspartic acid (D) at amino acid position 201 to be replaced by an asparagine (N). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Uncertain	0.38
Sift	Benign	0.070	.;T
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.79		Gain of MoRF binding (P = 0.0307);Gain of MoRF binding (P = 0.0307);
MVP		0.74
MPC		1.5
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.38
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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.

Other links and lift over

hg19: chr18-70461390;