rs10161149

Variant names:

• chr12-77681362-C-T
• rs10161149
• ENST00000550042.2:c.72+109096C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.96).
• 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 rank	MANE	Protein	UniProt
NAV3	XM_017020166.3	c.72+109096C>T		intron_variant	Intron 1 of 39		XP_016875655.1
NAV3	XM_017020167.1	c.72+109096C>T		intron_variant	Intron 1 of 38		XP_016875656.1
NAV3	XM_047429817.1	c.72+109096C>T		intron_variant	Intron 1 of 37		XP_047285773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.72+109096C>T		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

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

African (AFR) AF: 0.307 AC: 12705 AN: 41426

American (AMR) AF: 0.0945 AC: 1444 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3468

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5176

South Asian (SAS) AF: 0.0567 AC: 273 AN: 4818

European-Finnish (FIN) AF: 0.143 AC: 1511 AN: 10572

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0586 AC: 3985 AN: 67980

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.0750 Hom.: 1178

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
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs10161149; hg19: chr12-78075142;