chr12-77505730-G-A

Variant names:

• chr12-77505730-G-A
• rs17788937
• ENST00000550042.2:c.-336-66129G>A

Variant summary

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

The ENST00000550042.2(NAV3):​c.-336-66129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,022 control chromosomes in the GnomAD database, including 2,336 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 (2336 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.-336-66129G>A		intron	N/A	ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24805 AN: 151904 Hom.: 2337 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.163 AC: 24802 AN: 152022 Hom.: 2336 Cov.: 32 AF XY: 0.162 AC XY: 12027 AN XY: 74318

African (AFR) AF: 0.0823 AC: 3415 AN: 41482

American (AMR) AF: 0.235 AC: 3590 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5172

South Asian (SAS) AF: 0.187 AC: 901 AN: 4818

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13852 AN: 67940

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.189 Hom.: 6017

Bravo AF: 0.167

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.52
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs17788937; hg19: chr12-77899510;