ENST00000550042.2:c.72+5069G>C

Variant names:

• chr12-77577335-G-C
• rs902602
• ENST00000550042.2:c.72+5069G>C

Variant summary

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

The ENST00000550042.2(NAV3):​c.72+5069G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,020 control chromosomes in the GnomAD database, including 4,677 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 0.24 (4677 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	XM_017020166.3	c.72+5069G>C		intron_variant	Intron 1 of 39		XP_016875655.1
NAV3	XM_017020167.1	c.72+5069G>C		intron_variant	Intron 1 of 38		XP_016875656.1
NAV3	XM_047429817.1	c.72+5069G>C		intron_variant	Intron 1 of 37		XP_047285773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.72+5069G>C		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35896 AN: 151902 Hom.: 4684 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.236 AC: 35887 AN: 152020 Hom.: 4677 Cov.: 32 AF XY: 0.238 AC XY: 17656 AN XY: 74302

African (AFR) AF: 0.138 AC: 5747 AN: 41504

American (AMR) AF: 0.268 AC: 4094 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2321 AN: 5160

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2092 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18141 AN: 67916

Other (OTH) AF: 0.271 AC: 572 AN: 2108

Alfa AF: 0.238 Hom.: 572

Bravo AF: 0.238

Asia WGS AF: 0.337 AC: 1172 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.55
PhyloP100		-0.087

Splicing

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

Other links and lift over

dbSNP: rs902602; hg19: chr12-77971115;