rs300489

Positions:

• chr12-78092214-G-A
• chr12-78092214-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.2637-24558G>A		intron_variant		ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.2637-24558G>A		intron_variant		1	NM_001024383.2	ENSP00000381007
NAV3	ENST00000536525.6	c.2637-24558G>A		intron_variant		1		ENSP00000446132	P1
NAV3	ENST00000644176.1	c.1137-24558G>A		intron_variant				ENSP00000495503

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

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.326

Alfa AF: 0.296 Hom.: 10300

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

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

LitVar

Other links and lift over

dbSNP: rs300489; hg19: chr12-78485994;