Variant 12-77831636-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024383.2(NAV3):c.175A>C(p.Lys59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NAV3
NM_001024383.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.07854399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV3	NM_001024383.2 linkuse as main transcript	c.175A>C	p.Lys59Gln	missense_variant	1/40	ENST00000397909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV3	ENST00000397909.7 linkuse as main transcript	c.175A>C	p.Lys59Gln	missense_variant	1/40	1	NM_001024383.2		Q8IVL0-1
NAV3	ENST00000536525.6 linkuse as main transcript	c.175A>C	p.Lys59Gln	missense_variant	1/39	1		P1	Q8IVL0-2
NAV3	ENST00000549464.5 linkuse as main transcript	c.175A>C	p.Lys59Gln	missense_variant	1/10	5
NAV3	ENST00000550042.2 linkuse as main transcript	c.73-108683A>C		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249066

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.175A>C (p.K59Q) alteration is located in exon 1 (coding exon 1) of the NAV3 gene. This alteration results from a A to C substitution at nucleotide position 175, causing the lysine (K) at amino acid position 59 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.028

T;.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.75

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.97

.;L;L

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.087, 0.094

MutPred

0.24

Loss of ubiquitination at K59 (P = 0.0051);Loss of ubiquitination at K59 (P = 0.0051);Loss of ubiquitination at K59 (P = 0.0051);

MVP

0.14

MPC

0.58

ClinPred

0.085

GERP RS

0.16

Varity_R

0.16

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over