NM_001024383.2:c.2024-11718A>C

Variant names:

• chr12-78038275-A-C
• rs11107957
• NM_001024383.2:c.2024-11718A>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.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
• Publications: 5 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=-0.82).
• 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 rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.2024-11718A>C		intron_variant	Intron 9 of 39	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.2024-11718A>C		intron_variant	Intron 9 of 39	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.2024-11718A>C		intron_variant	Intron 9 of 38	1		ENSP00000446132.2
NAV3	ENST00000644176.1	c.523+889A>C		intron_variant	Intron 1 of 28			ENSP00000495503.1
NAV3	ENST00000549464.5	c.2024-11718A>C		intron_variant	Intron 9 of 9	5		ENSP00000446628.1

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

African (AFR) AF: 0.123 AC: 5101 AN: 41528

American (AMR) AF: 0.158 AC: 2417 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3470

East Asian (EAS) AF: 0.00770 AC: 40 AN: 5192

South Asian (SAS) AF: 0.121 AC: 583 AN: 4828

European-Finnish (FIN) AF: 0.249 AC: 2634 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18104 AN: 67968

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.238 Hom.: 2652

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
PhyloP100		1.9
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: rs11107957; hg19: chr12-78432055;