chr18-72794161-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138966.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO1	NM_138966.5	MANE Select	c.595G>T	p.Ala199Ser	missense	Exon 6 of 11	NP_620416.2	Q8TDF5-3
	NETO1	NM_001201465.3		c.595G>T	p.Ala199Ser	missense	Exon 6 of 11	NP_001188394.2	Q8TDF5-3
	NETO1	NM_001354017.2		c.595G>T	p.Ala199Ser	missense	Exon 6 of 11	NP_001340946.2	Q8TDF5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO1	ENST00000327305.11	TSL:1 MANE Select	c.595G>T	p.Ala199Ser	missense	Exon 6 of 11	ENSP00000313088.6	Q8TDF5-3
	NETO1	ENST00000583169.5	TSL:1	c.595G>T	p.Ala199Ser	missense	Exon 6 of 11	ENSP00000464312.1	Q8TDF5-3
	NETO1	ENST00000916241.1		c.595G>T	p.Ala199Ser	missense	Exon 6 of 12	ENSP00000586300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.096	T
Sift4G	Benign	0.17	T
Polyphen		0.59	P
Vest4		0.74
MutPred		0.62		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

Other links and lift over

hg19: chr18-70461396;