12-77609761-C-A

Variant names:

• chr12-77609761-C-A
• rs711114
• ENST00000550042.2:c.72+37495C>A

Variant summary

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

The ENST00000550042.2(NAV3):​c.72+37495C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,014 control chromosomes in the GnomAD database, including 739 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 0.092 (739 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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.72+37495C>A		intron	N/A	ENSP00000489639.1	A0A1B0GTC4

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13886 AN: 151896 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0915 AC: 13914 AN: 152014 Hom.: 739 Cov.: 32 AF XY: 0.0915 AC XY: 6796 AN XY: 74302

African (AFR) AF: 0.0678 AC: 2815 AN: 41520

American (AMR) AF: 0.0842 AC: 1281 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.0184 AC: 95 AN: 5154

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4822

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7339 AN: 67932

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.106 Hom.: 1664

Bravo AF: 0.0900

Asia WGS AF: 0.0630 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		-0.029

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: rs711114;

hg19: chr12-78003541;