chr18-72794161-C-A

Variant names:

• chr18-72794161-C-A
• NM_138966.5:c.595G>T

Variant summary

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

The NM_138966.5(NETO1):​c.595G>T​(p.Ala199Ser) 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)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NETO1	NM_138966.5	c.595G>T	p.Ala199Ser	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.595G>T	p.Ala199Ser	missense_variant	Exon 6 of 11	1	NM_138966.5	ENSP00000313088.6
NETO1	ENST00000583169.5	c.595G>T	p.Ala199Ser	missense_variant	Exon 6 of 11	1		ENSP00000464312.1
NETO1	ENST00000579730.2	n.303-10255G>T		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

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.595G>T (p.A199S) alteration is located in exon 6 (coding exon 6) of the NETO1 gene. This alteration results from a G to T substitution at nucleotide position 595, causing the alanine (A) at amino acid position 199 to be replaced by a serine (S). 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	Benign	0.17
BayesDel_addAF	Benign	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	.;N
REVEL	Benign	0.17
Sift	Benign	0.096	.;T
Sift4G	Benign	0.17	T;T
Polyphen		0.59	P;P
Vest4		0.74
MutPred		0.62		Gain of disorder (P = 0.0513);Gain of disorder (P = 0.0513);
MVP		0.48
MPC		1.2
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.14
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-70461396;