rs696460

Variant names:

• chr12-77622877-C-T
• rs696460
• ENST00000550042.2:c.72+50611C>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+50611C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,098 control chromosomes in the GnomAD database, including 2,796 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 0.16 (2796 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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+50611C>T		intron	N/A	ENSP00000489639.1	A0A1B0GTC4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24013 AN: 151980 Hom.: 2778 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.158 AC: 24081 AN: 152098 Hom.: 2796 Cov.: 32 AF XY: 0.154 AC XY: 11476 AN XY: 74372

African (AFR) AF: 0.324 AC: 13432 AN: 41448

American (AMR) AF: 0.102 AC: 1554 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3472

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5176

South Asian (SAS) AF: 0.0820 AC: 395 AN: 4818

European-Finnish (FIN) AF: 0.0935 AC: 990 AN: 10586

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.0974 AC: 6625 AN: 67990

Other (OTH) AF: 0.155 AC: 326 AN: 2110

Alfa AF: 0.132 Hom.: 252

Bravo AF: 0.169

Asia WGS AF: 0.0830 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.47
PhyloP100		-0.40

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: rs696460;

hg19: chr12-78016657;