rs10506772

Variant names:

• chr12-78148337-G-C
• rs10506772
• NM_001024383.2:c.4708-505G>C

Variant summary

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

The NM_001024383.2(NAV3):​c.4708-505G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 151,906 control chromosomes in the GnomAD database, including 660 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 0.086 (660 hom., cov: 32)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024383.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	NM_001024383.2	MANE Select	c.4708-505G>C		intron	N/A	NP_001019554.1	Q8IVL0-1
	NAV3	NM_014903.6		c.4708-505G>C		intron	N/A	NP_055718.4
	NAV3	NM_001438019.1		c.3166-505G>C		intron	N/A	NP_001424948.1	A0A2R8YFX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000397909.7	TSL:1 MANE Select	c.4708-505G>C		intron	N/A	ENSP00000381007.2	Q8IVL0-1
	NAV3	ENST00000536525.6	TSL:1	c.4708-505G>C		intron	N/A	ENSP00000446132.2	Q8IVL0-2
	NAV3	ENST00000552895.5	TSL:1	c.1390-505G>C		intron	N/A	ENSP00000446644.1	H0YHA8

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13057 AN: 151788 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0860 AC: 13068 AN: 151906 Hom.: 660 Cov.: 32 AF XY: 0.0838 AC XY: 6219 AN XY: 74212

African (AFR) AF: 0.132 AC: 5468 AN: 41430

American (AMR) AF: 0.0646 AC: 983 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5170

South Asian (SAS) AF: 0.135 AC: 651 AN: 4808

European-Finnish (FIN) AF: 0.0438 AC: 462 AN: 10552

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4622 AN: 67938

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0790 Hom.: 64

Bravo AF: 0.0888

Asia WGS AF: 0.0790 AC: 275 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.023
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: rs10506772; hg19: chr12-78542117;