Variant 12-77966309-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001024383.2(NAV3):c.487+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 1,605,342 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 102 hom. )

Consequence

NAV3
NM_001024383.2 splice_region, intron

Scores

Splicing: ADA: 0.0001151

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.929

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 12-77966309-A-G is Benign according to our data. Variant chr12-77966309-A-G is described in ClinVar as [Benign]. Clinvar id is 774821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAV3	NM_001024383.2 linkuse as main transcript	c.487+8A>G		splice_region_variant, intron_variant		ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7 linkuse as main transcript	c.487+8A>G		splice_region_variant, intron_variant		1	NM_001024383.2	ENSP00000381007		Q8IVL0-1

Frequencies

GnomAD3 genomes

AF:

0.00809

AC:

1231

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00987

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00924

AC:

2256

AN:

244214

Hom.:

AF XY:

0.00960

AC XY:

1269

AN XY:

132178

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0147

Gnomad FIN exome

AF:

0.0263

Gnomad NFE exome

AF:

0.00876

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00988

AC:

14358

AN:

1453060

Hom.:

102

Cov.:

AF XY:

0.0103

AC XY:

7439

AN XY:

722804

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.00962

Gnomad4 OTH exome

AF:

0.00881

GnomAD4 genome

AF:

0.00809

AC:

1232

AN:

152282

Hom.:

Cov.:

AF XY:

0.00907

AC XY:

675

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.00987

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00966

Hom.:

Bravo

AF:

0.00580

Asia WGS

AF:

0.00462

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.0

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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