rs695982

chr12-77608774-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000550042.2(NAV3):c.72+36508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,826 control chromosomes in the GnomAD database, including 8,538 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 0.33 (8538 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV3	XM_017020166.3	c.72+36508G>A		intron_variant
NAV3	XM_017020167.1	c.72+36508G>A		intron_variant
NAV3	XM_047429817.1	c.72+36508G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV3	ENST00000550042.2	c.72+36508G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49967 AN: 151704 Hom.: 8520 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.330 AC: 50038 AN: 151826 Hom.: 8538 Cov.: 32 AF XY: 0.330 AC XY: 24502 AN XY: 74204

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.367

Alfa AF: 0.363 Hom.: 9838

Bravo AF: 0.333

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.021
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs695982; hg19: chr12-78002554;