chr12-77396769-G-A

Variant names:

• chr12-77396769-G-A
• rs1465070
• ENST00000550042.2:c.-337+71555G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000550042.2(NAV3):​c.-337+71555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,960 control chromosomes in the GnomAD database, including 33,009 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 0.65 (33009 hom., cov: 31)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.-337+71555G>A		intron	N/A	ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99314 AN: 151842 Hom.: 32995 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.654 AC: 99356 AN: 151960 Hom.: 33009 Cov.: 31 AF XY: 0.645 AC XY: 47868 AN XY: 74262

African (AFR) AF: 0.605 AC: 25083 AN: 41438

American (AMR) AF: 0.621 AC: 9479 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2215 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2784 AN: 5150

South Asian (SAS) AF: 0.458 AC: 2205 AN: 4816

European-Finnish (FIN) AF: 0.614 AC: 6472 AN: 10544

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48808 AN: 67964

Other (OTH) AF: 0.689 AC: 1453 AN: 2110

Alfa AF: 0.702 Hom.: 63379

Bravo AF: 0.658

Asia WGS AF: 0.553 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs1465070; hg19: chr12-77790549;