NM_145117.5:c.155A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145117.5(NAV2):​c.155A>C​(p.Tyr52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y52C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NAV2
NM_145117.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.20
Variant links:
Genes affected
NAV2 (HGNC:15997): (neuron navigator 2) This gene encodes a member of the neuron navigator gene family, which may play a role in cellular growth and migration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
LEISA1 (HGNC:55264): (lncRNA enhancing IL-6/STAT3 signaling activation 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3114677).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAV2NM_145117.5 linkc.155A>C p.Tyr52Ser missense_variant Exon 1 of 38 ENST00000349880.9 NP_660093.2 Q8IVL1-3A7E2D6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAV2ENST00000349880.9 linkc.155A>C p.Tyr52Ser missense_variant Exon 1 of 38 1 NM_145117.5 ENSP00000309577.6 Q8IVL1-3
NAV2ENST00000360655.8 linkc.76-118634A>C intron_variant Intron 1 of 37 1 ENSP00000353871.4 Q8IVL1-4
NAV2ENST00000396087.7 linkc.155A>C p.Tyr52Ser missense_variant Exon 1 of 41 5 ENSP00000379396.3 Q8IVL1-1
NAV2ENST00000396085.6 linkc.155A>C p.Tyr52Ser missense_variant Exon 1 of 39 5 ENSP00000379394.1 Q8IVL1-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461290
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726940
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.021
.;.;T;.;T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.058
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.78
T;T;T;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.31
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.;.;N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.49
N;.;.;N;N
REVEL
Benign
0.26
Sift
Benign
0.031
D;.;.;D;D
Sift4G
Benign
0.15
T;T;T;T;T
Polyphen
0.95
.;.;.;P;.
Vest4
0.61
MutPred
0.27
Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);
MVP
0.043
MPC
0.79
ClinPred
0.68
D
GERP RS
2.9
Varity_R
0.11
gMVP
0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-19735396; API