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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550042.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.72+109096C>T		intron	N/A	ENSP00000489639.1	A0A1B0GTC4

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10161149;

hg19: chr12-78075142;