Genetic Variant NAV3:c.4683+119A>G (chr12-78140453-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001024383.2(NAV3):c.4683+119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 890,356 control chromosomes in the GnomAD database, including 51,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8829 hom., cov: 32)

Exomes 𝑓: 0.33 ( 42632 hom. )

Consequence

NAV3
NM_001024383.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.265

Publications

6 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2 link	c.4683+119A>G		intron_variant	Intron 20 of 39	ENST00000397909.7	NP_001019554.1	Q8IVL0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7 link	c.4683+119A>G		intron_variant	Intron 20 of 39	1	NM_001024383.2	ENSP00000381007.2		Q8IVL0-1

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50892

AN:

151884

Hom.:

8806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.397

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.329

AC:

243098

AN:

738354

Hom.:

42632

AF XY:

0.322

AC XY:

125628

AN XY:

389792

show subpopulations

African (AFR)

AF:

0.304

AC:

5703

AN:

18762

American (AMR)

AF:

0.561

AC:

19461

AN:

34678

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

4610

AN:

18796

East Asian (EAS)

AF:

0.467

AC:

16432

AN:

35174

South Asian (SAS)

AF:

0.240

AC:

15308

AN:

63762

European-Finnish (FIN)

AF:

0.398

AC:

14988

AN:

37692

Middle Eastern (MID)

AF:

0.280

AC:

1141

AN:

4078

European-Non Finnish (NFE)

AF:

0.314

AC:

153699

AN:

489248

Other (OTH)

AF:

0.325

AC:

11756

AN:

36164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7459

14918

22376

29835

37294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.335

AC:

50965

AN:

152002

Hom.:

8829

Cov.:

AF XY:

0.343

AC XY:

25445

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.302

AC:

12538

AN:

41474

American (AMR)

AF:

0.458

AC:

6990

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

879

AN:

3468

East Asian (EAS)

AF:

0.478

AC:

2460

AN:

5144

South Asian (SAS)

AF:

0.241

AC:

1162

AN:

4814

European-Finnish (FIN)

AF:

0.425

AC:

4489

AN:

10564

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21313

AN:

67970

Other (OTH)

AF:

0.330

AC:

698

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1715

3430

5145

6860

8575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.322

Hom.:

14563

Bravo

AF:

0.344

Asia WGS

AF:

0.379

AC:

1317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.70

(source)

DANN

Benign

0.59

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(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.

chr12-78140453-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over