Variant 1-201648912-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001389617.1(NAV1):c.1105G>A(p.Ala369Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,612,720 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 3 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.178

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, NAV1

BP4

Computational evidence support a benign effect (MetaRNN=0.0027803779).

BP6

Variant 1-201648912-G-A is Benign according to our data. Variant chr1-201648912-G-A is described in ClinVar as [Benign]. Clinvar id is 780295.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 478 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NAV1	NM_001389617.1 linkuse as main transcript	c.1105G>A	p.Ala369Thr	missense_variant	5/34	ENST00000685211.1
NAV1	NM_001389616.1 linkuse as main transcript	c.1105G>A	p.Ala369Thr	missense_variant	4/32
NAV1	NM_001389615.1 linkuse as main transcript	c.1105G>A	p.Ala369Thr	missense_variant	5/31
NAV1	NM_020443.5 linkuse as main transcript	c.244G>A	p.Ala82Thr	missense_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV1	ENST00000685211.1 linkuse as main transcript	c.1105G>A	p.Ala369Thr	missense_variant	5/34		NM_001389617.1	P2
NAV1	ENST00000367296.8 linkuse as main transcript	c.244G>A	p.Ala82Thr	missense_variant	1/30	5		A2	Q8NEY1-1
NAV1	ENST00000367302.5 linkuse as main transcript	c.283G>A	p.Ala95Thr	missense_variant	3/30	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

473

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000748

AC:

184

AN:

245988

Hom.:

AF XY:

0.000610

AC XY:

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000909

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000303

AC:

442

AN:

1460462

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.00314

AC:

478

AN:

152258

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000493

Hom.:

Bravo

AF:

0.00339

ESP6500AA

AF:

0.00978

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000958

AC:

116

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.037

Sift

Benign

0.31

T;T

Sift4G

Benign

0.52

T;T

Vest4

0.087

MVP

0.18

MPC

0.94

ClinPred

0.0034

GERP RS

1.0

Varity_R

0.074

gMVP

0.12

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