Genetic Variant NAV1:p.Pro520Ser (chr1-201649365-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001389617.1(NAV1):c.1558C>T(p.Pro520Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P520T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NAV1
NM_001389617.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.23

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33521932).

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.1558C>T	p.Pro520Ser	missense	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
NAV1	NM_001389616.1		c.1558C>T	p.Pro520Ser	missense	Exon 4 of 32	NP_001376545.1
NAV1	NM_001389615.1		c.1558C>T	p.Pro520Ser	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.1558C>T	p.Pro520Ser	missense	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
NAV1	ENST00000367296.8	TSL:5	c.697C>T	p.Pro233Ser	missense	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
NAV1	ENST00000367302.5	TSL:5	c.736C>T	p.Pro246Ser	missense	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33352

American (AMR)

AF:

0.00

AC:

AN:

44268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39420

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109278

Other (OTH)

AF:

0.00

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.094

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

PhyloP100

7.2

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.7

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Benign

0.73

Vest4

0.50

MutPred

0.30

Loss of sheet (P = 0.0025)

MVP

0.23

MPC

2.1

ClinPred

0.96

GERP RS

4.7

Varity_R

0.42

gMVP

0.72

Mutation Taster

=55/45

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over