rs11107957

Positions:

• chr12-78038275-A-C

Variant summary

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

The NM_001024383.2(NAV3):​c.2024-11718A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,164 control chromosomes in the GnomAD database, including 3,564 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 0.20 (3564 hom., cov: 32)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV3	NM_001024383.2	c.2024-11718A>C		intron_variant		ENST00000397909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV3	ENST00000397909.7	c.2024-11718A>C		intron_variant		1	NM_001024383.2
NAV3	ENST00000536525.6	c.2024-11718A>C		intron_variant		1		P1
NAV3	ENST00000549464.5	c.2024-11718A>C		intron_variant		5
NAV3	ENST00000644176.1	c.523+889A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30364 AN: 152046 Hom.: 3567 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00749

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.200 AC: 30360 AN: 152164 Hom.: 3564 Cov.: 32 AF XY: 0.195 AC XY: 14482 AN XY: 74388

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.00770

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.189

Alfa AF: 0.236 Hom.: 2388

Bravo AF: 0.189

Asia WGS AF: 0.0600 AC: 210 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.78

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: rs11107957; hg19: chr12-78432055;