12-77831497-G-C

Variant names:

• chr12-77831497-G-C
• rs1163802650
• NM_001024383.2:c.36G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024383.2(NAV3):​c.36G>C​(p.Gln12His) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q12Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAV3 NM_001024383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13296974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.36G>C	p.Gln12His	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.36G>C	p.Gln12His	missense_variant	Exon 1 of 40	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.36G>C	p.Gln12His	missense_variant	Exon 1 of 39	1		ENSP00000446132.2
NAV3	ENST00000549464.5	c.36G>C	p.Gln12His	missense_variant	Exon 1 of 10	5		ENSP00000446628.1
NAV3	ENST00000550042.2	c.73-108822G>C		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;L
PhyloP100		1.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.040
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.0	.;B;B
Vest4		0.20, 0.20
MutPred		0.19		Loss of MoRF binding (P = 0.0975);Loss of MoRF binding (P = 0.0975);Loss of MoRF binding (P = 0.0975);
MVP		0.21
MPC		0.29
ClinPred		0.67	D
GERP RS		3.6
PromoterAI		-0.10	Neutral
Varity_R		0.14
gMVP		0.56
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs1163802650; hg19: chr12-78225277;