Variant 1-201648717-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM2PP2BP4_StrongBS2

The NM_001389617.1(NAV1):c.910A>G(p.Ser304Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000394 in 1,267,758 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: not found (cov: 32)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.203

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 Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, NAV1

BP4

Computational evidence support a benign effect (MetaRNN=0.036170483).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NAV1	NM_001389617.1 linkuse as main transcript	c.910A>G	p.Ser304Gly	missense_variant	5/34	ENST00000685211.1
NAV1	NM_001389616.1 linkuse as main transcript	c.910A>G	p.Ser304Gly	missense_variant	4/32
NAV1	NM_001389615.1 linkuse as main transcript	c.910A>G	p.Ser304Gly	missense_variant	5/31
NAV1	NM_020443.5 linkuse as main transcript	c.49A>G	p.Ser17Gly	missense_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV1	ENST00000685211.1 linkuse as main transcript	c.910A>G	p.Ser304Gly	missense_variant	5/34		NM_001389617.1	P2
NAV1	ENST00000367296.8 linkuse as main transcript	c.49A>G	p.Ser17Gly	missense_variant	1/30	5		A2	Q8NEY1-1
NAV1	ENST00000367302.5 linkuse as main transcript	c.88A>G	p.Ser30Gly	missense_variant	3/30	5		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000394

AC:

AN:

1267758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

622344

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:

0.00000488

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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.49A>G (p.S17G) alteration is located in exon 1 (coding exon 1) of the NAV1 gene. This alteration results from a A to G substitution at nucleotide position 49, causing the serine (S) at amino acid position 17 to be replaced by a glycine (G). 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

0.046

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.9

DANN

Benign

0.52

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.085

Sift

Benign

0.99

T;T

Sift4G

Benign

0.10

T;T

Vest4

0.092

MutPred

0.10

.;Loss of glycosylation at S17 (P = 0.0046);

MVP

0.11

MPC

0.89

ClinPred

0.037

GERP RS

1.3

Varity_R

0.053

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over