rs756634630

Variant summary

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

The NM_002499.4(NEO1):ā€‹c.613A>Gā€‹(p.Met205Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,876 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: 31)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

NEO1
NM_002499.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88
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 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=0.09153652).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEO1NM_002499.4 linkc.613A>G p.Met205Val missense_variant Exon 3 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.613A>G p.Met205Val missense_variant Exon 3 of 29 1 NM_002499.4 ENSP00000261908.6 Q92859-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251392
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135868
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:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727242
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:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.049
T;T;.;.
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.38
N
LIST_S2
Uncertain
0.92
.;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.092
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.88
N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.40
N;N;N;N
REVEL
Benign
0.074
Sift
Uncertain
0.017
D;D;D;D
Sift4G
Uncertain
0.033
D;D;D;D
Polyphen
0.0
B;B;.;.
Vest4
0.080
MutPred
0.45
Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP
0.23
MPC
0.19
ClinPred
0.12
T
GERP RS
1.7
Varity_R
0.16
gMVP
0.41

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: rs756634630; hg19: chr15-73415030; API