chr1-201718569-T-A

Variant summary

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

The NM_001389617.1(NAV1):​c.1901T>A​(p.Met634Lys) 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 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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. M634T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75
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)

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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.1901T>A p.Met634Lys 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.1901T>A p.Met634Lys missense_variant Exon 7 of 34 NM_001389617.1 ENSP00000510803.1 A0A8I5KSE4
NAV1ENST00000367296.8 linkc.1040T>A p.Met347Lys missense_variant Exon 3 of 30 5 ENSP00000356265.4 Q8NEY1-1
NAV1ENST00000367302.5 linkc.1079T>A p.Met360Lys missense_variant Exon 5 of 30 5 ENSP00000356271.1 A0A0A0MRJ3
IPO9-AS1ENST00000413035.5 linkn.685-30156A>T intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461746
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727186
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.044
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.045
.;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.68
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;N
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.24
Sift
Uncertain
0.0040
D;D
Sift4G
Benign
0.19
T;T
Vest4
0.78
MutPred
0.31
.;Gain of ubiquitination at M347 (P = 0.0094);
MVP
0.36
MPC
1.5
ClinPred
0.31
T
GERP RS
4.5
Varity_R
0.53
gMVP
0.57

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: chr1-201687697; API