rs372725432

Variant names:

• chr12-77940365-A-C
• rs372725432
• NM_001024383.2:c.290A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-77940365-A-C
• chr12-77940365-A-G
• chr12-77940365-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001024383.2(NAV3):​c.290A>C​(p.Lys97Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K97R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAV3 NM_001024383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2931351).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024383.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	NM_001024383.2	MANE Select	c.290A>C	p.Lys97Thr	missense	Exon 2 of 40	NP_001019554.1	Q8IVL0-1
	NAV3	NM_014903.6		c.290A>C	p.Lys97Thr	missense	Exon 2 of 39	NP_055718.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV3	ENST00000397909.7	TSL:1 MANE Select	c.290A>C	p.Lys97Thr	missense	Exon 2 of 40	ENSP00000381007.2	Q8IVL0-1
	NAV3	ENST00000536525.6	TSL:1	c.290A>C	p.Lys97Thr	missense	Exon 2 of 39	ENSP00000446132.2	Q8IVL0-2
	NAV3	ENST00000549464.5	TSL:5	c.290A>C	p.Lys97Thr	missense	Exon 2 of 10	ENSP00000446628.1	F8VZV4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.012	D
Polyphen		0.68	P
Vest4		0.47
MutPred		0.45		Loss of methylation at K97 (P = 0.0407)
MVP		0.39
MPC		0.57
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.38
Mutation Taster		=78/22	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: rs372725432; hg19: chr12-78334145;