Variant 1-201718569-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001389617.1(NAV1):c.1901T>C(p.Met634Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Variant links:

Genes affected

NAV1 (HGNC:15989): (neuron navigator 1) 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. The exact function of this gene is not known, but it is thought to play a role in in neuronal development and regeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

NAV1 links:

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

IPO9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09759197).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAV1	NM_001389617.1 linkuse as main transcript	c.1901T>C	p.Met634Thr	missense_variant	7/34	ENST00000685211.1	NP_001376546.1
IPO9-AS1	NR_046696.1 linkuse as main transcript	n.685-30156A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1 linkuse as main transcript	c.1901T>C	p.Met634Thr	missense_variant	7/34		NM_001389617.1	ENSP00000510803	P2
IPO9-AS1	ENST00000413035.5 linkuse as main transcript	n.685-30156A>G		intron_variant, non_coding_transcript_variant		3
NAV1	ENST00000367296.8 linkuse as main transcript	c.1040T>C	p.Met347Thr	missense_variant	3/30	5		ENSP00000356265	A2	Q8NEY1-1
NAV1	ENST00000367302.5 linkuse as main transcript	c.1079T>C	p.Met360Thr	missense_variant	5/30	5		ENSP00000356271	A2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250808

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

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:

0.00000547

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

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

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

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 30, 2024

The c.1040T>C (p.M347T) alteration is located in exon 3 (coding exon 3) of the NAV1 gene. This alteration results from a T to C substitution at nucleotide position 1040, causing the methionine (M) at amino acid position 347 to be replaced by a threonine (T). 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

0.076

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.037

.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

.;N

MutationTaster

Benign

0.93

N;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.074

Sift

Benign

0.16

T;T

Sift4G

Benign

0.34

T;T

Vest4

0.57

MVP

0.10

MPC

1.1

ClinPred

0.0083

GERP RS

4.5

Varity_R

0.047

gMVP

0.32

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