Genetic Variant NAV1:p.Gly328Ala (chr1-201648790-G-C) – 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.983G>C(p.Gly328Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

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=0.12292278).

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.983G>C	p.Gly328Ala	missense	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
NAV1	NM_001389616.1		c.983G>C	p.Gly328Ala	missense	Exon 4 of 32	NP_001376545.1
NAV1	NM_001389615.1		c.983G>C	p.Gly328Ala	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.983G>C	p.Gly328Ala	missense	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
NAV1	ENST00000367296.8	TSL:5	c.122G>C	p.Gly41Ala	missense	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
NAV1	ENST00000367302.5	TSL:5	c.161G>C	p.Gly54Ala	missense	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

113314

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1361040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670066

African (AFR)

AF:

0.00

AC:

AN:

30426

American (AMR)

AF:

0.00

AC:

AN:

31330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22292

East Asian (EAS)

AF:

0.00

AC:

AN:

35236

South Asian (SAS)

AF:

0.00

AC:

AN:

72674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067754

Other (OTH)

AF:

0.00

AC:

AN:

56690

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.014

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PhyloP100

0.15

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.14

REVEL

Benign

0.062

Sift

Uncertain

0.028

Sift4G

Benign

0.50

Vest4

0.12

MutPred

0.13

Loss of loop (P = 0.0128)

MVP

0.17

MPC

1.0

ClinPred

0.074

GERP RS

-0.11

Varity_R

0.087

gMVP

0.25

Mutation Taster

=88/12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over