1-201648808-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001389617.1(NAV1):c.1001C>G(p.Ala334Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000062 in 1,563,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, NAV1

BP4

Computational evidence support a benign effect (MetaRNN=0.09037539).

BS2

High AC in GnomAdExome at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NAV1	NM_001389617.1 linkuse as main transcript	c.1001C>G	p.Ala334Gly	missense_variant	5/34	ENST00000685211.1
NAV1	NM_001389616.1 linkuse as main transcript	c.1001C>G	p.Ala334Gly	missense_variant	4/32
NAV1	NM_001389615.1 linkuse as main transcript	c.1001C>G	p.Ala334Gly	missense_variant	5/31
NAV1	NM_020443.5 linkuse as main transcript	c.140C>G	p.Ala47Gly	missense_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV1	ENST00000685211.1 linkuse as main transcript	c.1001C>G	p.Ala334Gly	missense_variant	5/34		NM_001389617.1	P2
NAV1	ENST00000367296.8 linkuse as main transcript	c.140C>G	p.Ala47Gly	missense_variant	1/30	5		A2	Q8NEY1-1
NAV1	ENST00000367302.5 linkuse as main transcript	c.179C>G	p.Ala60Gly	missense_variant	3/30	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000815

AC:

AN:

171850

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

95426

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 SAS exome

AF:

0.000375

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000550

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000666

AC:

AN:

1411542

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

698540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000265

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000323

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000560

Gnomad4 OTH exome

AF:

0.0000856

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000368

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.140C>G (p.A47G) alteration is located in exon 1 (coding exon 1) of the NAV1 gene. This alteration results from a C to G substitution at nucleotide position 140, causing the alanine (A) at amino acid position 47 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.63

N;N;N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.039

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.38

T;T

Vest4

0.15

MutPred

0.18

.;Gain of relative solvent accessibility (P = 0.0082);

MVP

0.19

MPC

1.6

ClinPred

0.10

GERP RS

4.7

Varity_R

0.15

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over