chr12-78092214-G-A

Variant names:

• chr12-78092214-G-A
• rs300489
• NM_001024383.2:c.2637-24558G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024383.2(NAV3):​c.2637-24558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,826 control chromosomes in the GnomAD database, including 8,069 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 0.32 (8069 hom., cov: 31)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.2637-24558G>A		intron_variant	Intron 12 of 39	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.2637-24558G>A		intron_variant	Intron 12 of 39	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.2637-24558G>A		intron_variant	Intron 12 of 38	1		ENSP00000446132.2
NAV3	ENST00000644176.1	c.1137-24558G>A		intron_variant	Intron 4 of 28			ENSP00000495503.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48829 AN: 151708 Hom.: 8049 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48886 AN: 151826 Hom.: 8069 Cov.: 31 AF XY: 0.321 AC XY: 23825 AN XY: 74210

African (AFR) AF: 0.386 AC: 15959 AN: 41372

American (AMR) AF: 0.293 AC: 4465 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.104 AC: 538 AN: 5154

South Asian (SAS) AF: 0.329 AC: 1583 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3047 AN: 10498

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21108 AN: 67948

Other (OTH) AF: 0.326 AC: 686 AN: 2104

Alfa AF: 0.304 Hom.: 23925

Bravo AF: 0.320

Asia WGS AF: 0.195 AC: 681 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs300489; hg19: chr12-78485994;