rs778591775

Variant names:

• chr1-201718640-C-A
• rs778591775
• NM_001389617.1:c.1972C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-201718640-C-A
• chr1-201718640-C-G
• chr1-201718640-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001389617.1(NAV1):​c.1972C>A​(p.Arg658Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R658C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.44

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]

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.1972C>A	p.Arg658Ser	missense_variant	Exon 7 of 34	ENST00000685211.1	NP_001376546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.1972C>A	p.Arg658Ser	missense_variant	Exon 7 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.1111C>A	p.Arg371Ser	missense_variant	Exon 3 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.1150C>A	p.Arg384Ser	missense_variant	Exon 5 of 30	5		ENSP00000356271.1
IPO9-AS1	ENST00000413035.5	n.685-30227G>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.22
Sift	Benign	0.091	T;T
Sift4G	Benign	0.55	T;T
Vest4		0.75
MutPred		0.27		.;Loss of sheet (P = 0.0063);
MVP		0.21
MPC		0.65
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.25
gMVP		0.48

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

Other links and lift over

dbSNP: rs778591775; hg19: chr1-201687768;