ENST00000550042.2:c.72+37495C>A

Variant names:

• chr12-77609761-C-A
• rs711114
• ENST00000550042.2:c.72+37495C>A

Variant summary

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

The ENST00000550042.2(NAV3):​c.72+37495C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,014 control chromosomes in the GnomAD database, including 739 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 0.092 (739 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	XM_017020166.3	c.72+37495C>A		intron_variant	Intron 1 of 39		XP_016875655.1
NAV3	XM_017020167.1	c.72+37495C>A		intron_variant	Intron 1 of 38		XP_016875656.1
NAV3	XM_047429817.1	c.72+37495C>A		intron_variant	Intron 1 of 37		XP_047285773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.72+37495C>A		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13886 AN: 151896 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0915 AC: 13914 AN: 152014 Hom.: 739 Cov.: 32 AF XY: 0.0915 AC XY: 6796 AN XY: 74302

African (AFR) AF: 0.0678 AC: 2815 AN: 41520

American (AMR) AF: 0.0842 AC: 1281 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.0184 AC: 95 AN: 5154

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4822

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7339 AN: 67932

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.106 Hom.: 1664

Bravo AF: 0.0900

Asia WGS AF: 0.0630 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		-0.029

Splicing

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

Other links and lift over

dbSNP: rs711114; hg19: chr12-78003541;