12-77925752-A-G

Variant names:

• chr12-77925752-A-G
• rs1479024
• NM_001024383.2:c.244-14567A>G

Variant summary

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

The NM_001024383.2(NAV3):​c.244-14567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,982 control chromosomes in the GnomAD database, including 9,513 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 0.35 (9513 hom., cov: 31)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.244-14567A>G		intron_variant	Intron 1 of 39	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.244-14567A>G		intron_variant	Intron 1 of 39	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.244-14567A>G		intron_variant	Intron 1 of 38	1		ENSP00000446132.2
NAV3	ENST00000549464.5	c.244-14567A>G		intron_variant	Intron 1 of 9	5		ENSP00000446628.1
NAV3	ENST00000550042.2	c.73-14567A>G		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52547 AN: 151864 Hom.: 9504 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.346 AC: 52580 AN: 151982 Hom.: 9513 Cov.: 31 AF XY: 0.343 AC XY: 25444 AN XY: 74274

African (AFR) AF: 0.250 AC: 10353 AN: 41442

American (AMR) AF: 0.366 AC: 5577 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2220 AN: 5152

South Asian (SAS) AF: 0.392 AC: 1884 AN: 4810

European-Finnish (FIN) AF: 0.281 AC: 2970 AN: 10572

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.396 AC: 26934 AN: 67976

Other (OTH) AF: 0.397 AC: 840 AN: 2114

Alfa AF: 0.353 Hom.: 1286

Bravo AF: 0.346

Asia WGS AF: 0.372 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		0.079
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: rs1479024; hg19: chr12-78319532;