Genetic Variant NAV1:p.Ala334Asp (chr1-201648808-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001389617.1(NAV1):c.1001C>A(p.Ala334Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,411,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A334S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.07

Publications

0 publications found

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]

NAV1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24924794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389617.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAV1	NM_001389617.1	MANE Select	c.1001C>A	p.Ala334Asp	missense	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
NAV1	NM_001389616.1		c.1001C>A	p.Ala334Asp	missense	Exon 4 of 32	NP_001376545.1
NAV1	NM_001389615.1		c.1001C>A	p.Ala334Asp	missense	Exon 5 of 31	NP_001376544.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAV1	ENST00000685211.1	MANE Select	c.1001C>A	p.Ala334Asp	missense	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
NAV1	ENST00000367296.8	TSL:5	c.140C>A	p.Ala47Asp	missense	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
NAV1	ENST00000367302.5	TSL:5	c.179C>A	p.Ala60Asp	missense	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000582

AC:

AN:

171850

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1411542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32424

American (AMR)

AF:

0.0000265

AC:

AN:

37766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24360

East Asian (EAS)

AF:

0.00

AC:

AN:

38260

South Asian (SAS)

AF:

0.00

AC:

AN:

80582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089754

Other (OTH)

AF:

0.00

AC:

AN:

58432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

PhyloP100

4.1

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.58

REVEL

Benign

0.087

Sift

Uncertain

0.0010

Sift4G

Benign

0.096

Vest4

0.30

MutPred

0.26

Gain of loop (P = 0.024)

MVP

0.14

MPC

2.4

ClinPred

0.60

GERP RS

4.7

Varity_R

0.44

gMVP

0.55

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over