12-77356770-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.954

Alfa AF: 0.939 Hom.: 63084

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1918215; hg19: chr12-77750550;