1-201648808-C-G

Variant names:

• chr1-201648808-C-G
• rs776139888
• NM_001389617.1:c.1001C>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.1001C>G​(p.Ala334Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000062 in 1,563,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A334S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09037539).
• BS2: High AC in GnomAdExome4 at 94 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.1001C>G	p.Ala334Gly	missense	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.1001C>G	p.Ala334Gly	missense	Exon 4 of 32	NP_001376545.1
	NAV1	NM_001389615.1		c.1001C>G	p.Ala334Gly	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.1001C>G	p.Ala334Gly	missense	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367296.8	TSL:5	c.140C>G	p.Ala47Gly	missense	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
	NAV1	ENST00000367302.5	TSL:5	c.179C>G	p.Ala60Gly	missense	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000815 AC: 14 AN: 171850 AF XY: 0.000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000550

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000666 AC: 94 AN: 1411542 Hom.: 0 Cov.: 54 AF XY: 0.0000888 AC XY: 62 AN XY: 698540

African (AFR) AF: 0.00 AC: 0 AN: 32424

American (AMR) AF: 0.0000265 AC: 1 AN: 37766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24360

East Asian (EAS) AF: 0.00 AC: 0 AN: 38260

South Asian (SAS) AF: 0.000323 AC: 26 AN: 80582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44398

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5566

European-Non Finnish (NFE) AF: 0.0000560 AC: 61 AN: 1089754

Other (OTH) AF: 0.0000856 AC: 5 AN: 58432

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000368 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3472

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	0.070
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.040
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.039
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.38	T
Vest4		0.15
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.19
MPC		1.6
ClinPred		0.10	T
GERP RS		4.7
Varity_R		0.15
gMVP		0.25
Mutation Taster		=81/19	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: rs776139888; hg19: chr1-201617936;