rs6538140

Variant names:

• chr12-77344225-G-A
• rs6538140
• ENST00000550042.2:c.-337+19011G>A

Variant summary

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

The ENST00000550042.2(NAV3):​c.-337+19011G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,034 control chromosomes in the GnomAD database, including 28,666 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 0.61 (28666 hom., cov: 33)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 7 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.-337+19011G>A		intron_variant	Intron 1 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93115 AN: 151916 Hom.: 28635 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.613 AC: 93196 AN: 152034 Hom.: 28666 Cov.: 33 AF XY: 0.616 AC XY: 45773 AN XY: 74306

African (AFR) AF: 0.663 AC: 27490 AN: 41478

American (AMR) AF: 0.635 AC: 9690 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1795 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2794 AN: 5164

South Asian (SAS) AF: 0.648 AC: 3129 AN: 4826

European-Finnish (FIN) AF: 0.585 AC: 6177 AN: 10562

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40193 AN: 67952

Other (OTH) AF: 0.579 AC: 1222 AN: 2112

Alfa AF: 0.597 Hom.: 91996

Bravo AF: 0.619

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.1
DANN	Benign	0.65
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs6538140; hg19: chr12-77738005;