12-77831693-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001024383.2(NAV3):c.232G>C(p.Glu78Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000249 in 1,605,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

NAV3
NM_001024383.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.24

Publications

2 publications found

Variant links:

Genes affected

NAV3 (HGNC:15998): (neuron navigator 3) 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. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined. [provided by RefSeq, Jul 2008]

NAV3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

NAV3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20151174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2 link	c.232G>C	p.Glu78Gln	missense_variant	Exon 1 of 40	ENST00000397909.7	NP_001019554.1	Q8IVL0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NAV3	ENST00000397909.7 link	c.232G>C	p.Glu78Gln	missense_variant	Exon 1 of 40	1	NM_001024383.2	ENSP00000381007.2	Q8IVL0-1
NAV3	ENST00000536525.6 link	c.232G>C	p.Glu78Gln	missense_variant	Exon 1 of 39	1		ENSP00000446132.2	Q8IVL0-2
NAV3	ENST00000549464.5 link	c.232G>C	p.Glu78Gln	missense_variant	Exon 1 of 10	5		ENSP00000446628.1	F8VZV4
NAV3	ENST00000550042.2 link	c.73-108626G>C		intron_variant	Intron 2 of 8	5		ENSP00000489639.1	A0A1B0GTC4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152196

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000167

AC:

AN:

239912

AF XY:

0.0000154

show subpopulations

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:

0.0000363

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1453708

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

722904

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32884

American (AMR)

AF:

0.00

AC:

AN:

42882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25504

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

84644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1109408

Other (OTH)

AF:

0.00

AC:

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.232G>C (p.E78Q) alteration is located in exon 1 (coding exon 1) of the NAV3 gene. This alteration results from a G to C substitution at nucleotide position 232, causing the glutamic acid (E) at amino acid position 78 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.20

.;N;N

PhyloP100

6.2

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.83, 0.73

.;P;P

Vest4

0.29, 0.29

MutPred

0.45

Loss of ubiquitination at K77 (P = 0.04);Loss of ubiquitination at K77 (P = 0.04);Loss of ubiquitination at K77 (P = 0.04);

MVP

0.64

MPC

0.20

ClinPred

0.50

GERP RS

4.4

PromoterAI

-0.090

Neutral

(source)

Varity_R

0.22

gMVP

0.28

Mutation Taster

=87/13

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.

12-77831693-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over