Genetic Variant NM_001024383.2: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

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NM_001024383.2:c.4683+119A>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