NM_001024383.2:c.194G>A

Variant names:

• chr12-77831655-G-A
• NM_001024383.2:c.194G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024383.2(NAV3):​c.194G>A​(p.Gly65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAV3 NM_001024383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113461375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.194G>A	p.Gly65Glu	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.194G>A	p.Gly65Glu	missense_variant	Exon 1 of 40	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.194G>A	p.Gly65Glu	missense_variant	Exon 1 of 39	1		ENSP00000446132.2
NAV3	ENST00000549464.5	c.194G>A	p.Gly65Glu	missense_variant	Exon 1 of 10	5		ENSP00000446628.1
NAV3	ENST00000550042.2	c.73-108664G>A		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.080
Sift	Benign	0.049	D;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.11, 0.11
MutPred		0.28		Gain of ubiquitination at K67 (P = 0.0314);Gain of ubiquitination at K67 (P = 0.0314);Gain of ubiquitination at K67 (P = 0.0314);
MVP		0.13
MPC		0.18
ClinPred		0.28	T
GERP RS		3.7
Varity_R		0.075
gMVP		0.18

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: chr12-78225435;