NM_001024383.2:c.77T>G

Variant names:

• chr12-77831538-T-G
• NM_001024383.2:c.77T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001024383.2(NAV3):​c.77T>G​(p.Ile26Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAV3 NM_001024383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.77T>G	p.Ile26Arg	missense_variant	Exon 1 of 40	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.77T>G	p.Ile26Arg	missense_variant	Exon 1 of 40	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.77T>G	p.Ile26Arg	missense_variant	Exon 1 of 39	1		ENSP00000446132.2
NAV3	ENST00000549464.5	c.77T>G	p.Ile26Arg	missense_variant	Exon 1 of 10	5		ENSP00000446628.1
NAV3	ENST00000550042.2	c.73-108781T>G		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;T;T
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.5	.;L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0, 0.99	.;D;D
Vest4		0.54, 0.58
MutPred		0.46		Gain of catalytic residue at I26 (P = 0.0061);Gain of catalytic residue at I26 (P = 0.0061);Gain of catalytic residue at I26 (P = 0.0061);
MVP		0.59
MPC		0.51
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-78225318;