NM_001389617.1:c.2083A>G

Variant names:

• chr1-201718751-A-G
• rs1672243039
• NM_001389617.1:c.2083A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001389617.1(NAV1):​c.2083A>G​(p.Thr695Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,453,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T695T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21399951).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

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.2083A>G	p.Thr695Ala	missense	Exon 7 of 34	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.2083A>G	p.Thr695Ala	missense	Exon 6 of 32	NP_001376545.1
	NAV1	NM_001389615.1		c.2083A>G	p.Thr695Ala	missense	Exon 7 of 31	NP_001376544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	ENST00000685211.1	MANE Select	c.2083A>G	p.Thr695Ala	missense	Exon 7 of 34	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000855601.1		c.1291A>G	p.Thr431Ala	missense	Exon 6 of 32	ENSP00000525660.1
	NAV1	ENST00000935746.1		c.1291A>G	p.Thr431Ala	missense	Exon 5 of 31	ENSP00000605805.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1453834 Hom.: 0 Cov.: 32 AF XY: 0.00000970 AC XY: 7 AN XY: 721558

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.00 AC: 0 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1105860

Other (OTH) AF: 0.00 AC: 0 AN: 60026

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.0030
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.15	T
Vest4		0.63
MutPred		0.16		Loss of glycosylation at T408 (P = 0.0151)
MVP		0.22
MPC		0.40
ClinPred		0.71	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.33
Mutation Taster		=94/6	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: rs1672243039; hg19: chr1-201687879;