1-201648912-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001389617.1(NAV1):​c.1105G>A​(p.Ala369Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,612,720 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 3 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

2
16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.178
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0027803779).
BP6
Variant 1-201648912-G-A is Benign according to our data. Variant chr1-201648912-G-A is described in ClinVar as [Benign]. Clinvar id is 780295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 478 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAV1NM_001389617.1 linkuse as main transcriptc.1105G>A p.Ala369Thr missense_variant 5/34 ENST00000685211.1 NP_001376546.1
NAV1NM_001389616.1 linkuse as main transcriptc.1105G>A p.Ala369Thr missense_variant 4/32 NP_001376545.1
NAV1NM_001389615.1 linkuse as main transcriptc.1105G>A p.Ala369Thr missense_variant 5/31 NP_001376544.1
NAV1NM_020443.5 linkuse as main transcriptc.244G>A p.Ala82Thr missense_variant 1/30 NP_065176.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAV1ENST00000685211.1 linkuse as main transcriptc.1105G>A p.Ala369Thr missense_variant 5/34 NM_001389617.1 ENSP00000510803 P2
NAV1ENST00000367296.8 linkuse as main transcriptc.244G>A p.Ala82Thr missense_variant 1/305 ENSP00000356265 A2Q8NEY1-1
NAV1ENST00000367302.5 linkuse as main transcriptc.283G>A p.Ala95Thr missense_variant 3/305 ENSP00000356271 A2

Frequencies

GnomAD3 genomes
AF:
0.00311
AC:
473
AN:
152144
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0108
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.000748
AC:
184
AN:
245988
Hom.:
3
AF XY:
0.000610
AC XY:
82
AN XY:
134434
show subpopulations
Gnomad AFR exome
AF:
0.0113
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000909
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.000303
AC:
442
AN:
1460462
Hom.:
3
Cov.:
54
AF XY:
0.000267
AC XY:
194
AN XY:
726548
show subpopulations
Gnomad4 AFR exome
AF:
0.0114
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.000547
GnomAD4 genome
AF:
0.00314
AC:
478
AN:
152258
Hom.:
2
Cov.:
32
AF XY:
0.00293
AC XY:
218
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0109
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.000493
Hom.:
2
Bravo
AF:
0.00339
ESP6500AA
AF:
0.00978
AC:
43
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000958
AC:
116
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.019
.;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.76
T;T
MetaRNN
Benign
0.0028
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.2
.;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.32
N;N
REVEL
Benign
0.037
Sift
Benign
0.31
T;T
Sift4G
Benign
0.52
T;T
Vest4
0.087
MVP
0.18
MPC
0.94
ClinPred
0.0034
T
GERP RS
1.0
Varity_R
0.074
gMVP
0.12

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: rs144867483; hg19: chr1-201618040; API