12-77975746-A-T

Variant names:

• chr12-77975746-A-T
• rs998070
• NM_001024383.2:c.671+7044A>T

Variant summary

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

The NM_001024383.2(NAV3):​c.671+7044A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,096 control chromosomes in the GnomAD database, including 11,423 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 0.37 (11423 hom., cov: 33)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024383.2. 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
	NAV3	NM_001024383.2	MANE Select	c.671+7044A>T		intron	N/A	NP_001019554.1
	NAV3	NM_014903.6		c.671+7044A>T		intron	N/A	NP_055718.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000397909.7	TSL:1 MANE Select	c.671+7044A>T		intron	N/A	ENSP00000381007.2
	NAV3	ENST00000536525.6	TSL:1	c.671+7044A>T		intron	N/A	ENSP00000446132.2
	NAV3	ENST00000549464.5	TSL:5	c.671+7044A>T		intron	N/A	ENSP00000446628.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56870 AN: 151978 Hom.: 11417 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.374 AC: 56887 AN: 152096 Hom.: 11423 Cov.: 33 AF XY: 0.373 AC XY: 27762 AN XY: 74350

African (AFR) AF: 0.222 AC: 9195 AN: 41510

American (AMR) AF: 0.436 AC: 6660 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2175 AN: 5166

South Asian (SAS) AF: 0.442 AC: 2134 AN: 4824

European-Finnish (FIN) AF: 0.381 AC: 4029 AN: 10582

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29967 AN: 67964

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.390 Hom.: 1494

Bravo AF: 0.371

Asia WGS AF: 0.407 AC: 1411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs998070; hg19: chr12-78369526;