Genetic Variant NM_001389617.1:c.1517C>A (chr1-201649324-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001389617.1(NAV1):c.1517C>A(p.Ser506Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000014 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13733056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389617.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAV1	NM_001389617.1	MANE Select	c.1517C>A	p.Ser506Tyr	missense	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
NAV1	NM_001389616.1		c.1517C>A	p.Ser506Tyr	missense	Exon 4 of 32	NP_001376545.1
NAV1	NM_001389615.1		c.1517C>A	p.Ser506Tyr	missense	Exon 5 of 31	NP_001376544.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAV1	ENST00000685211.1	MANE Select	c.1517C>A	p.Ser506Tyr	missense	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
NAV1	ENST00000367296.8	TSL:5	c.656C>A	p.Ser219Tyr	missense	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
NAV1	ENST00000367302.5	TSL:5	c.695C>A	p.Ser232Tyr	missense	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460038

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111666

Other (OTH)

AF:

0.0000166

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

2.2

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.0

REVEL

Benign

0.064

Sift

Uncertain

0.011

Sift4G

Uncertain

0.028

Vest4

0.21

MutPred

0.18

Loss of relative solvent accessibility (P = 0.0186)

MVP

0.13

MPC

1.3

ClinPred

0.23

GERP RS

4.7

Varity_R

0.17

gMVP

0.21

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over