chr1-201781148-G-T

Variant names:

• chr1-201781148-G-T
• NM_001389617.1:c.2363G>T

Variant summary

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

The NM_001389617.1(NAV1):​c.2363G>T​(p.Arg788Leu) 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 1,461,892 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. R788Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

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=0.35414526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.2363G>T	p.Arg788Leu	missense_variant	Exon 9 of 34	ENST00000685211.1	NP_001376546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.2363G>T	p.Arg788Leu	missense_variant	Exon 9 of 34		NM_001389617.1	ENSP00000510803.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.87, 0.99	.;P;D
Vest4		0.41
MutPred		0.21		.;Loss of MoRF binding (P = 0.0363);.;
MVP		0.24
MPC		1.2
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.47
gMVP		0.41

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: chr1-201750276;