12-77335605-C-T

Variant names:

• chr12-77335605-C-T
• rs1402279
• ENST00000550042.2:c.-337+10391C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.-337+10391C>T		intron_variant	Intron 1 of 8	5		ENSP00000489639.1

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;