12-78140453-A-G

Position:

• chr12-78140453-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024383.2(NAV3):​c.4683+119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 890,356 control chromosomes in the GnomAD database, including 51,461 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 0.34 (8829 hom., cov: 32)
  • Exomes 𝑓: 0.33 (42632 hom.)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.4683+119A>G		intron_variant		ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.4683+119A>G		intron_variant		1	NM_001024383.2	ENSP00000381007.2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50892 AN: 151884 Hom.: 8806 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.329 AC: 243098 AN: 738354 Hom.: 42632 AF XY: 0.322 AC XY: 125628 AN XY: 389792

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.335 AC: 50965 AN: 152002 Hom.: 8829 Cov.: 32 AF XY: 0.343 AC XY: 25445 AN XY: 74270

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.330

Alfa AF: 0.319 Hom.: 4131

Bravo AF: 0.344

Asia WGS AF: 0.379 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.70
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1726427; hg19: chr12-78534233; COSMIC: COSV57095298;