12-77389580-G-A

Variant names:

• chr12-77389580-G-A
• rs1405539
• XR_007063383.1:n.5673G>A

Variant summary

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

The XR_007063383.1(LOC124902972):​n.5673G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,858 control chromosomes in the GnomAD database, including 21,354 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 0.52 (21354 hom., cov: 32)
• Consequence: LOC124902972 XR_007063383.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 1 publications found

Genes affected

LOC124902972 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.-337+64366G>A		intron	N/A	ENSP00000489639.1
	ENSG00000257835	ENST00000552736.3	TSL:3	n.262-891G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78380 AN: 151742 Hom.: 21355 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.516 AC: 78380 AN: 151858 Hom.: 21354 Cov.: 32 AF XY: 0.510 AC XY: 37873 AN XY: 74210

African (AFR) AF: 0.344 AC: 14242 AN: 41372

American (AMR) AF: 0.532 AC: 8115 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1905 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2392 AN: 5164

South Asian (SAS) AF: 0.393 AC: 1889 AN: 4806

European-Finnish (FIN) AF: 0.556 AC: 5864 AN: 10542

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42112 AN: 67930

Other (OTH) AF: 0.547 AC: 1157 AN: 2114

Alfa AF: 0.588 Hom.: 12664

Bravo AF: 0.511

Asia WGS AF: 0.438 AC: 1521 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.027
DANN	Benign	0.18
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs1405539; hg19: chr12-77783360;