15-73126429-T-C

Variant summary

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

The NM_002499.4(NEO1):ā€‹c.737T>Cā€‹(p.Ile246Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000625 in 1,440,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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 š‘“: 0.0000062 ( 0 hom. )

Consequence

NEO1
NM_002499.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.228
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]

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=0.055993408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEO1NM_002499.4 linkc.737T>C p.Ile246Thr missense_variant Exon 4 of 29 ENST00000261908.11 NP_002490.2 Q92859-1Q59FP8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEO1ENST00000261908.11 linkc.737T>C p.Ile246Thr missense_variant Exon 4 of 29 1 NM_002499.4 ENSP00000261908.6 Q92859-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000209
AC:
5
AN:
239354
Hom.:
0
AF XY:
0.00000773
AC XY:
1
AN XY:
129380
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000156
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000625
AC:
9
AN:
1440344
Hom.:
0
Cov.:
32
AF XY:
0.00000698
AC XY:
5
AN XY:
716750
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000212
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000416
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
5.9
DANN
Benign
0.38
DEOGEN2
Benign
0.054
T;T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.0039
N
LIST_S2
Benign
0.015
.;T;T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.056
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.070
N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
1.1
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.59
T;T;T;T
Sift4G
Benign
0.66
T;T;T;T
Polyphen
0.0
B;B;.;.
Vest4
0.079
MutPred
0.47
Gain of disorder (P = 0.025);Gain of disorder (P = 0.025);Gain of disorder (P = 0.025);Gain of disorder (P = 0.025);
MVP
0.043
MPC
0.23
ClinPred
0.022
T
GERP RS
4.7
Varity_R
0.020
gMVP
0.36

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.

Other links and lift over

dbSNP: rs780801893; hg19: chr15-73418770; API