rs1405539

Positions:

• chr12-77389580-G-A
• chr12-77389580-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902972	XR_007063383.1	n.5673G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000552736.2	n.254-891G>A		intron_variant, non_coding_transcript_variant		3
NAV3	ENST00000550042.2	c.-337+64366G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.547

Alfa AF: 0.585 Hom.: 11226

Bravo AF: 0.511

Asia WGS AF: 0.438 AC: 1521 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1405539; hg19: chr12-77783360;