Genetic Variant NM_002499.4:c.44C>T (chr15-73052719-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002499.4(NEO1):c.44C>T(p.Ser15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S15Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEO1
NM_002499.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

0 publications found

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 was made for transcript

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=0.21267417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002499.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEO1	NM_002499.4	MANE Select	c.44C>T	p.Ser15Phe	missense	Exon 1 of 29	NP_002490.2	Q92859-1
NEO1	NM_001419531.1		c.44C>T	p.Ser15Phe	missense	Exon 2 of 30	NP_001406460.1
NEO1	NM_001172624.2		c.44C>T	p.Ser15Phe	missense	Exon 2 of 29	NP_001166095.1	Q92859-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEO1	ENST00000261908.11	TSL:1 MANE Select	c.44C>T	p.Ser15Phe	missense	Exon 1 of 29	ENSP00000261908.6	Q92859-1
NEO1	ENST00000558964.5	TSL:1	c.44C>T	p.Ser15Phe	missense	Exon 1 of 28	ENSP00000453200.1	Q92859-4
NEO1	ENST00000560262.5	TSL:1	c.44C>T	p.Ser15Phe	missense	Exon 1 of 28	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1207832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

595256

African (AFR)

AF:

0.00

AC:

AN:

24658

American (AMR)

AF:

0.00

AC:

AN:

21990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19324

East Asian (EAS)

AF:

0.00

AC:

AN:

24746

South Asian (SAS)

AF:

0.00

AC:

AN:

57348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

980346

Other (OTH)

AF:

0.00

AC:

AN:

47218

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.040

REVEL

Benign

0.081

Sift

Benign

0.077

Sift4G

Uncertain

0.025

Polyphen

0.68

Vest4

0.27

MutPred

0.48

Loss of sheet (P = 3e-04)

MVP

0.58

MPC

0.20

ClinPred

0.12

GERP RS

0.013

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.069

gMVP

0.43

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over