rs10506772

Positions:

• chr12-78148337-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397909.7(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 ENST00000397909.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.4708-505G>C		intron_variant		ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.4708-505G>C		intron_variant		1	NM_001024383.2	ENSP00000381007

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.106

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.56

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: rs10506772; hg19: chr12-78542117;