rs1351349628

Variant names:

• chr1-201649365-C-A
• rs1351349628
• NM_001389617.1:c.1558C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-201649365-C-A
• chr1-201649365-C-G
• chr1-201649365-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001389617.1(NAV1):​c.1558C>A​(p.Pro520Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	NM_001389617.1	MANE Select	c.1558C>A	p.Pro520Thr	missense	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.1558C>A	p.Pro520Thr	missense	Exon 4 of 32	NP_001376545.1
	NAV1	NM_001389615.1		c.1558C>A	p.Pro520Thr	missense	Exon 5 of 31	NP_001376544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	ENST00000685211.1	MANE Select	c.1558C>A	p.Pro520Thr	missense	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367296.8	TSL:5	c.697C>A	p.Pro233Thr	missense	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
	NAV1	ENST00000367302.5	TSL:5	c.736C>A	p.Pro246Thr	missense	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454892 Hom.: 0 Cov.: 55 AF XY: 0.00000138 AC XY: 1 AN XY: 723160

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 85426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109278

Other (OTH) AF: 0.00 AC: 0 AN: 60090

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.58	T
Vest4		0.59
MutPred		0.39		Gain of sheet (P = 0.0073)
MVP		0.20
MPC		2.2
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.51
gMVP		0.71
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs1351349628; hg19: chr1-201618493;