12-77354045-A-G

Variant names:

• chr12-77354045-A-G
• rs7958647
• ENST00000550042.2:c.-337+28831A>G

Variant summary

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

The ENST00000550042.2(NAV3):​c.-337+28831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,206 control chromosomes in the GnomAD database, including 68,840 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 0.95 (68840 hom., cov: 31)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.-337+28831A>G		intron	N/A	ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144590 AN: 152088 Hom.: 68779 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.958

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

GnomAD4 genome AF: 0.951 AC: 144710 AN: 152206 Hom.: 68840 Cov.: 31 AF XY: 0.954 AC XY: 70952 AN XY: 74392

African (AFR) AF: 0.949 AC: 39410 AN: 41516

American (AMR) AF: 0.961 AC: 14677 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3302 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5161 AN: 5164

South Asian (SAS) AF: 0.982 AC: 4733 AN: 4820

European-Finnish (FIN) AF: 0.972 AC: 10312 AN: 10608

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63913 AN: 68028

Other (OTH) AF: 0.959 AC: 2027 AN: 2114

Alfa AF: 0.944 Hom.: 36081

Bravo AF: 0.949

Asia WGS AF: 0.990 AC: 3440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.67
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs7958647; hg19: chr12-77747825;