Variant 15-73135919-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002499.4(NEO1):c.907G>A(p.Gly303Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000407 in 1,595,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

NEO1
NM_002499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.095884025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEO1	NM_002499.4 linkuse as main transcript	c.907G>A	p.Gly303Ser	missense_variant	5/29	ENST00000261908.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEO1	ENST00000261908.11 linkuse as main transcript	c.907G>A	p.Gly303Ser	missense_variant	5/29	1	NM_002499.4	A2	Q92859-1
NEO1	ENST00000558964.5 linkuse as main transcript	c.907G>A	p.Gly303Ser	missense_variant	5/28	1		P4	Q92859-4
NEO1	ENST00000560262.5 linkuse as main transcript	c.907G>A	p.Gly303Ser	missense_variant	5/28	1			Q92859-3
NEO1	ENST00000339362.9 linkuse as main transcript	c.907G>A	p.Gly303Ser	missense_variant	6/30	5		A2	Q92859-1

Frequencies

GnomAD3 genomes

AF:

0.000357

AC:

AN:

148510

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000667

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000295

AC:

AN:

240634

Hom.:

AF XY:

0.000284

AC XY:

AN XY:

130202

show subpopulations

Gnomad AFR exome

AF:

0.0000635

Gnomad AMR exome

AF:

0.0000905

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000151

Gnomad NFE exome

AF:

0.000566

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000412

AC:

596

AN:

1446762

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

281

AN XY:

719192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.000140

Gnomad4 NFE exome

AF:

0.000516

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000357

AC:

AN:

148612

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

AN XY:

72218

show subpopulations

Gnomad4 AFR

AF:

0.000149

Gnomad4 AMR

AF:

0.0000671

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000104

Gnomad4 NFE

AF:

0.000667

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000646

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000231

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

Feb 02, 2022

The c.907G>A (p.G303S) alteration is located in exon 5 (coding exon 5) of the NEO1 gene. This alteration results from a G to A substitution at nucleotide position 907, causing the glycine (G) at amino acid position 303 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;.;.

Eigen

Benign

-0.065

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

.;T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.096

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.0090

B;B;.;.

Vest4

0.33

MVP

0.27

MPC

0.45

ClinPred

0.12

GERP RS

3.9

Varity_R

0.11

gMVP

0.77

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