12-77827388-G-A

Variant names:

• chr12-77827388-G-A
• rs7977620
• ENST00000550042.2:c.73-112931G>A

Variant summary

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

The ENST00000550042.2(NAV3):​c.73-112931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,574 control chromosomes in the GnomAD database, including 8,235 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 0.31 (8235 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550042.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.73-112931G>A		intron	N/A	ENSP00000489639.1	A0A1B0GTC4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46918 AN: 151460 Hom.: 8241 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.309 AC: 46905 AN: 151574 Hom.: 8235 Cov.: 32 AF XY: 0.313 AC XY: 23148 AN XY: 74052

African (AFR) AF: 0.134 AC: 5534 AN: 41298

American (AMR) AF: 0.344 AC: 5227 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3468

East Asian (EAS) AF: 0.434 AC: 2223 AN: 5126

South Asian (SAS) AF: 0.285 AC: 1370 AN: 4802

European-Finnish (FIN) AF: 0.431 AC: 4504 AN: 10444

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25908 AN: 67922

Other (OTH) AF: 0.307 AC: 646 AN: 2104

Alfa AF: 0.354 Hom.: 20593

Bravo AF: 0.300

Asia WGS AF: 0.312 AC: 1084 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.036
DANN	Benign	0.34
PhyloP100		-0.91

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7977620;

hg19: chr12-78221168;