12-77335605-C-T

Position:

• chr12-77335605-C-T

Variant summary

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

The ENST00000550042.2(NAV3):​c.-337+10391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,294 control chromosomes in the GnomAD database, including 65,118 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 0.92 (65118 hom., cov: 33)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.-337+10391C>T		intron_variant		5		ENSP00000489639

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140478 AN: 152174 Hom.: 65082 Cov.: 33

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.923 AC: 140572 AN: 152294 Hom.: 65118 Cov.: 33 AF XY: 0.927 AC XY: 69077 AN XY: 74478

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.923

Alfa AF: 0.943 Hom.: 104957

Bravo AF: 0.917

Asia WGS AF: 0.923 AC: 3210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.075
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1402279; hg19: chr12-77729385;