Variant chr1-201648720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001389617.1(NAV1):c.913G>A(p.Gly305Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,259,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000010 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.437

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06183088).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NAV1	NM_001389617.1 linkuse as main transcript	c.913G>A	p.Gly305Ser	missense_variant	5/34	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1 linkuse as main transcript	c.913G>A	p.Gly305Ser	missense_variant	4/32		NP_001376545.1
NAV1	NM_001389615.1 linkuse as main transcript	c.913G>A	p.Gly305Ser	missense_variant	5/31		NP_001376544.1
NAV1	NM_020443.5 linkuse as main transcript	c.52G>A	p.Gly18Ser	missense_variant	1/30		NP_065176.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1 linkuse as main transcript	c.913G>A	p.Gly305Ser	missense_variant	5/34		NM_001389617.1	ENSP00000510803	P2
NAV1	ENST00000367296.8 linkuse as main transcript	c.52G>A	p.Gly18Ser	missense_variant	1/30	5		ENSP00000356265	A2	Q8NEY1-1
NAV1	ENST00000367302.5 linkuse as main transcript	c.91G>A	p.Gly31Ser	missense_variant	3/30	5		ENSP00000356271	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000590

AC:

AN:

50854

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

30116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000911

Gnomad FIN exome

AF:

0.000234

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1259206

Hom.:

Cov.:

AF XY:

0.00000810

AC XY:

AN XY:

617300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000532

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000509

Gnomad4 FIN exome

AF:

0.0000622

Gnomad4 NFE exome

AF:

0.00000687

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000837

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

Apr 07, 2023

The c.52G>A (p.G18S) alteration is located in exon 1 (coding exon 1) of the NAV1 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by a serine (S). 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

0.085

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.73

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.072

Sift

Benign

0.066

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.22

MutPred

0.14

.;Gain of glycosylation at G18 (P = 0.0047);

MVP

0.16

MPC

2.1

ClinPred

0.12

GERP RS

1.3

Varity_R

0.046

gMVP

0.15

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