rs10161149

chr12-77681362-C-T

Variant summary

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

The ENST00000550042.2(NAV3):c.72+109096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,032 control chromosomes in the GnomAD database, including 2,295 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 0.14 (2295 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV3	XM_017020166.3	c.72+109096C>T		intron_variant
NAV3	XM_017020167.1	c.72+109096C>T		intron_variant
NAV3	XM_047429817.1	c.72+109096C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV3	ENST00000550042.2	c.72+109096C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20586 AN: 151914 Hom.: 2290 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.136 AC: 20628 AN: 152032 Hom.: 2295 Cov.: 32 AF XY: 0.137 AC XY: 10156 AN XY: 74328

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.0567

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0706 Hom.: 793

Bravo AF: 0.139

Asia WGS AF: 0.0650 AC: 224 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.2
Dann	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10161149; hg19: chr12-78075142;