rs6538140

Positions:

• chr12-77344225-G-A

Variant summary

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

The ENST00000550042.2(NAV3):​c.-337+19011G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,034 control chromosomes in the GnomAD database, including 28,666 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 0.61 (28666 hom., cov: 33)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV3	ENST00000550042.2	c.-337+19011G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93115 AN: 151916 Hom.: 28635 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.613 AC: 93196 AN: 152034 Hom.: 28666 Cov.: 33 AF XY: 0.616 AC XY: 45773 AN XY: 74306

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.579

Alfa AF: 0.592 Hom.: 54920

Bravo AF: 0.619

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.1
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6538140; hg19: chr12-77738005;