18-72864831-C-A

Variant names:

• chr18-72864831-C-A
• rs780552539
• NM_138966.5:c.197G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001354018.2(NETO1):​c.-382G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NETO1 NM_001354018.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22958606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354018.2. 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.197G>T	p.Arg66Leu	missense	Exon 3 of 11	NP_620416.2	Q8TDF5-3
	NETO1	NM_001354018.2		c.-382G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001340947.2
	NETO1	NM_001201465.3		c.197G>T	p.Arg66Leu	missense	Exon 3 of 11	NP_001188394.2	Q8TDF5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO1	ENST00000327305.11	TSL:1 MANE Select	c.197G>T	p.Arg66Leu	missense	Exon 3 of 11	ENSP00000313088.6	Q8TDF5-3
	NETO1	ENST00000583169.5	TSL:1	c.197G>T	p.Arg66Leu	missense	Exon 3 of 11	ENSP00000464312.1	Q8TDF5-3
	NETO1	ENST00000397929.5	TSL:1	c.194G>T	p.Arg65Leu	missense	Exon 3 of 5	ENSP00000381024.1	Q8TDF5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461296 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726940

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111850

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.45	N
PhyloP100		2.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Uncertain	0.033	D
Polyphen		0.065	B
Vest4		0.66
MutPred		0.50		Loss of disorder (P = 0.0791)
MVP		0.59
MPC		0.92
ClinPred		0.88	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.69
Mutation Taster		=71/29	polymorphism

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

dbSNP: rs780552539; hg19: chr18-70532066;