Variant 15-73116684-T-C 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.275T>C(p.Phe92Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,912 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NEO1
NM_002499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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=0.18273282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEO1	NM_002499.4 linkuse as main transcript	c.275T>C	p.Phe92Ser	missense_variant	2/29	ENST00000261908.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEO1	ENST00000261908.11 linkuse as main transcript	c.275T>C	p.Phe92Ser	missense_variant	2/29	1	NM_002499.4	A2	Q92859-1
NEO1	ENST00000558964.5 linkuse as main transcript	c.275T>C	p.Phe92Ser	missense_variant	2/28	1		P4	Q92859-4
NEO1	ENST00000560262.5 linkuse as main transcript	c.275T>C	p.Phe92Ser	missense_variant	2/28	1			Q92859-3
NEO1	ENST00000339362.9 linkuse as main transcript	c.275T>C	p.Phe92Ser	missense_variant	3/30	5		A2	Q92859-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 10, 2022

The c.275T>C (p.F92S) alteration is located in exon 2 (coding exon 2) of the NEO1 gene. This alteration results from a T to C substitution at nucleotide position 275, causing the phenylalanine (F) at amino acid position 92 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

0.42

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.67

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.069

T;T;T;T

Polyphen

0.014

B;B;.;.

Vest4

0.38

MutPred

0.35

Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);

MVP

0.13

MPC

0.38

ClinPred

0.92

GERP RS

4.8

Varity_R

0.46

gMVP

0.55

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