1-201718455-A-C

Variant names:

• chr1-201718455-A-C
• rs1571904470
• NM_001389617.1:c.1787A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001389617.1(NAV1):​c.1787A>C​(p.Asn596Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. N596S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31335086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.1787A>C	p.Asn596Thr	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.1787A>C	p.Asn596Thr	missense_variant	Exon 7 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.926A>C	p.Asn309Thr	missense_variant	Exon 3 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.965A>C	p.Asn322Thr	missense_variant	Exon 5 of 30	5		ENSP00000356271.1
IPO9-AS1	ENST00000413035.5	n.685-30042T>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.42	T;T
Vest4		0.54
MutPred		0.083		.;Gain of glycosylation at N309 (P = 0.0217);
MVP		0.32
MPC		2.1
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.097
gMVP		0.56

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: rs1571904470; hg19: chr1-201687583;