chr12-78138574-C-G

Variant names:

• chr12-78138574-C-G
• rs10506771
• NM_001024383.2:c.4630+1209C>G

Variant summary

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

The NM_001024383.2(NAV3):​c.4630+1209C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,118 control chromosomes in the GnomAD database, including 992 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 0.11 (992 hom., cov: 32)
• Consequence: NAV3 NM_001024383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.4630+1209C>G		intron_variant	Intron 19 of 39	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.4630+1209C>G		intron_variant	Intron 19 of 39	1	NM_001024383.2	ENSP00000381007.2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16481 AN: 152000 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.108 AC: 16498 AN: 152118 Hom.: 992 Cov.: 32 AF XY: 0.109 AC XY: 8086 AN XY: 74364

African (AFR) AF: 0.0817 AC: 3390 AN: 41514

American (AMR) AF: 0.101 AC: 1535 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1327 AN: 5160

South Asian (SAS) AF: 0.112 AC: 540 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1094 AN: 10584

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7836 AN: 67994

Other (OTH) AF: 0.108 AC: 227 AN: 2104

Alfa AF: 0.112 Hom.: 122

Bravo AF: 0.110

Asia WGS AF: 0.153 AC: 528 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.59
PhyloP100		2.7
Mutation Taster		=99/1	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: rs10506771; hg19: chr12-78532354;