rs1271257

Variant names:

• chr12-77967528-G-C
• rs1271257
• NM_001024383.2:c.488-991G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024383.2(NAV3):​c.488-991G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,038 control chromosomes in the GnomAD database, including 48,840 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 0.80 (48840 hom., cov: 31)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 1 publications found

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]

NAV3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.488-991G>C		intron_variant	Intron 4 of 39	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.488-991G>C		intron_variant	Intron 4 of 39	1	NM_001024383.2	ENSP00000381007.2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121619 AN: 151918 Hom.: 48830 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.800 AC: 121673 AN: 152038 Hom.: 48840 Cov.: 31 AF XY: 0.802 AC XY: 59614 AN XY: 74330

African (AFR) AF: 0.749 AC: 31086 AN: 41484

American (AMR) AF: 0.811 AC: 12397 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2700 AN: 3462

East Asian (EAS) AF: 0.981 AC: 5079 AN: 5176

South Asian (SAS) AF: 0.828 AC: 3991 AN: 4822

European-Finnish (FIN) AF: 0.816 AC: 8650 AN: 10600

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55014 AN: 67888

Other (OTH) AF: 0.799 AC: 1691 AN: 2116

Alfa AF: 0.801 Hom.: 6052

Bravo AF: 0.798

Asia WGS AF: 0.854 AC: 2962 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.079
DANN	Benign	0.54
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1271257; hg19: chr12-78361308;