Variant 15-73052719-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002499.4(NEO1):c.44C>A(p.Ser15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,358,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

NEO1
NM_002499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

NEO1 (HGNC:7754): (neogenin 1) This gene encodes a cell surface protein that is a member of the immunoglobulin superfamily. The encoded protein consists of four N-terminal immunoglobulin-like domains, six fibronectin type III domains, a transmembrane domain and a C-terminal internal domain that shares homology with the tumor suppressor candidate gene DCC. This protein may be involved in cell growth and differentiation and in cell-cell adhesion. Defects in this gene are associated with cell proliferation in certain cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

NEO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05181977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEO1	NM_002499.4 linkuse as main transcript	c.44C>A	p.Ser15Tyr	missense_variant	1/29	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11 linkuse as main transcript	c.44C>A	p.Ser15Tyr	missense_variant	1/29	1	NM_002499.4	ENSP00000261908	A2	Q92859-1
NEO1	ENST00000558964.5 linkuse as main transcript	c.44C>A	p.Ser15Tyr	missense_variant	1/28	1		ENSP00000453200	P4	Q92859-4
NEO1	ENST00000560262.5 linkuse as main transcript	c.44C>A	p.Ser15Tyr	missense_variant	1/28	1		ENSP00000453317		Q92859-3
NEO1	ENST00000339362.9 linkuse as main transcript	c.44C>A	p.Ser15Tyr	missense_variant	2/30	5		ENSP00000341198	A2	Q92859-1

Frequencies

GnomAD3 genomes

AF:

0.0000731

AC:

AN:

150452

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

79972

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

46976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000149

AC:

180

AN:

1207832

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

103

AN XY:

595256

show subpopulations

Gnomad4 AFR exome

AF:

0.0000406

Gnomad4 AMR exome

AF:

0.0000455

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:

0.000176

Gnomad4 OTH exome

AF:

0.000106

GnomAD4 genome

AF:

0.0000731

AC:

AN:

150560

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73522

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ExAC

AF:

0.000167

AC:

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

May 08, 2023

The c.44C>A (p.S15Y) alteration is located in exon 1 (coding exon 1) of the NEO1 gene. This alteration results from a C to A substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 to be replaced by a tyrosine (Y). 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

0.25

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T;.;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.78

.;T;T;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.052

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.040

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.070

T;T;T;T

Sift4G

Uncertain

0.032

D;D;D;D

Polyphen

0.88

P;P;.;.

Vest4

0.29

MutPred

0.47

Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);

MVP

0.60

MPC

0.26

ClinPred

0.054

GERP RS

0.013

Varity_R

0.066

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over