Variant chr1-201648756-G-T 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_001389617.1(NAV1):c.949G>T(p.Ala317Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,401,932 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.786

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:

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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=0.105915815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NAV1	NM_001389617.1 linkuse as main transcript	c.949G>T	p.Ala317Ser	missense_variant	5/34	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1 linkuse as main transcript	c.949G>T	p.Ala317Ser	missense_variant	4/32		NP_001376545.1
NAV1	NM_001389615.1 linkuse as main transcript	c.949G>T	p.Ala317Ser	missense_variant	5/31		NP_001376544.1
NAV1	NM_020443.5 linkuse as main transcript	c.88G>T	p.Ala30Ser	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.949G>T	p.Ala317Ser	missense_variant	5/34		NM_001389617.1	ENSP00000510803	P2
NAV1	ENST00000367296.8 linkuse as main transcript	c.88G>T	p.Ala30Ser	missense_variant	1/30	5		ENSP00000356265	A2	Q8NEY1-1
NAV1	ENST00000367302.5 linkuse as main transcript	c.127G>T	p.Ala43Ser	missense_variant	3/30	5		ENSP00000356271	A2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.00e-7

AC:

AN:

1249994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

611632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000194

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151938

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

Jan 03, 2024

The c.88G>T (p.A30S) alteration is located in exon 1 (coding exon 1) of the NAV1 gene. This alteration results from a G to T substitution at nucleotide position 88, causing the alanine (A) at amino acid position 30 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

0.082

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.69

T;T

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.039

Sift

Benign

0.24

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.081

MutPred

0.15

.;Gain of phosphorylation at A30 (P = 0.0013);

MVP

0.27

MPC

0.89

ClinPred

0.059

GERP RS

2.5

Varity_R

0.067

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