chr1-201718442-T-A

Variant names:

• chr1-201718442-T-A
• NM_001389617.1:c.1774T>A

Variant summary

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

The NM_001389617.1(NAV1):​c.1774T>A​(p.Ser592Thr) 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

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=0.33983958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.1774T>A	p.Ser592Thr	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.1774T>A	p.Ser592Thr	missense_variant	Exon 7 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.913T>A	p.Ser305Thr	missense_variant	Exon 3 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.952T>A	p.Ser318Thr	missense_variant	Exon 5 of 30	5		ENSP00000356271.1
IPO9-AS1	ENST00000413035.5	n.685-30029A>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.913T>A (p.S305T) alteration is located in exon 3 (coding exon 3) of the NAV1 gene. This alteration results from a T to A substitution at nucleotide position 913, causing the serine (S) at amino acid position 305 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.090
Sift	Benign	0.32	T;T
Sift4G	Benign	0.42	T;T
Vest4		0.55
MutPred		0.13		.;Loss of sheet (P = 0.0457);
MVP		0.50
MPC		2.0
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.14
gMVP		0.63

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.

Other links and lift over

hg19: chr1-201687570;