1-201718640-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001389617.1(NAV1):​c.1972C>G​(p.Arg658Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R658C) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

NAV1
NM_001389617.1 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.44
Variant links:
Genes affected
NAV1 (HGNC:15989): (neuron navigator 1) This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. The exact function of this gene is not known, but it is thought to play a role in in neuronal development and regeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]
IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAV1NM_001389617.1 linkc.1972C>G p.Arg658Gly missense_variant Exon 7 of 34 ENST00000685211.1 NP_001376546.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAV1ENST00000685211.1 linkc.1972C>G p.Arg658Gly missense_variant Exon 7 of 34 NM_001389617.1 ENSP00000510803.1 A0A8I5KSE4
NAV1ENST00000367296.8 linkc.1111C>G p.Arg371Gly missense_variant Exon 3 of 30 5 ENSP00000356265.4 Q8NEY1-1
NAV1ENST00000367302.5 linkc.1150C>G p.Arg384Gly missense_variant Exon 5 of 30 5 ENSP00000356271.1 A0A0A0MRJ3
IPO9-AS1ENST00000413035.5 linkn.685-30227G>C intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
32
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
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74348
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Uncertain
0.089
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.048
.;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.5
.;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.31
Sift
Benign
0.077
T;T
Sift4G
Benign
0.066
T;T
Vest4
0.80
MutPred
0.25
.;Loss of sheet (P = 0.0104);
MVP
0.25
MPC
0.79
ClinPred
0.83
D
GERP RS
5.6
Varity_R
0.20
gMVP
0.49

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: rs778591775; hg19: chr1-201687768; API