rs1527047

Variant names:

• chr12-77379769-A-G
• rs1527047
• ENST00000550042.2:c.-337+54555A>G

Variant summary

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

The ENST00000552736.3(ENSG00000257835):​n.8A>G 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 0.568 in 151,934 control chromosomes in the GnomAD database, including 24,927 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 0.57 (24927 hom., cov: 31)
  • Exomes 𝑓: 0.43 (0 hom.)
• Consequence: ENSG00000257835 ENST00000552736.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• Publications: 1 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

ENSG00000257835 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000552736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000550042.2	TSL:5	c.-337+54555A>G		intron	N/A	ENSP00000489639.1	A0A1B0GTC4
	ENSG00000257835	ENST00000552736.3	TSL:3	n.8A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86337 AN: 151802 Hom.: 24931 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.568 AC: 86354 AN: 151920 Hom.: 24927 Cov.: 31 AF XY: 0.561 AC XY: 41679 AN XY: 74244

African (AFR) AF: 0.527 AC: 21806 AN: 41406

American (AMR) AF: 0.546 AC: 8341 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1907 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2376 AN: 5146

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4820

European-Finnish (FIN) AF: 0.556 AC: 5859 AN: 10540

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42220 AN: 67946

Other (OTH) AF: 0.584 AC: 1236 AN: 2116

Alfa AF: 0.602 Hom.: 14121

Bravo AF: 0.570

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.73
PhyloP100		-0.68

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1527047;

hg19: chr12-77773549;