ENST00000550042.2:c.-337+31556T>C

Variant names:

• chr12-77356770-T-C
• rs1918215
• ENST00000550042.2:c.-337+31556T>C

Variant summary

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

The ENST00000550042.2(NAV3):​c.-337+31556T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,280 control chromosomes in the GnomAD database, including 67,967 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 0.94 (67967 hom., cov: 32)
• Consequence: NAV3 ENST00000550042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000550042.2	c.-337+31556T>C		intron_variant	Intron 1 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143711 AN: 152162 Hom.: 67920 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.944 AC: 143817 AN: 152280 Hom.: 67967 Cov.: 32 AF XY: 0.948 AC XY: 70600 AN XY: 74472

African (AFR) AF: 0.928 AC: 38532 AN: 41542

American (AMR) AF: 0.958 AC: 14651 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3293 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5174

South Asian (SAS) AF: 0.982 AC: 4743 AN: 4832

European-Finnish (FIN) AF: 0.972 AC: 10320 AN: 10618

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

European-Non Finnish (NFE) AF: 0.939 AC: 63914 AN: 68034

Other (OTH) AF: 0.954 AC: 2016 AN: 2114

Alfa AF: 0.940 Hom.: 93097

Bravo AF: 0.941

Asia WGS AF: 0.989 AC: 3437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.78
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs1918215; hg19: chr12-77750550;