NM_001389617.1:c.1329C>T

Variant names:

• chr1-201649136-C-T
• rs1267119
• NM_001389617.1:c.1329C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001389617.1(NAV1):​c.1329C>T​(p.Gly443Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,611,722 control chromosomes in the GnomAD database, including 4,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (526 hom., cov: 33)
  • Exomes 𝑓: 0.072 (4088 hom.)
• Consequence: NAV1 NM_001389617.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.488
• Publications: 5 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-201649136-C-T is Benign according to our data. Variant chr1-201649136-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.488 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

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.1329C>T	p.Gly443Gly	synonymous	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.1329C>T	p.Gly443Gly	synonymous	Exon 4 of 32	NP_001376545.1
	NAV1	NM_001389615.1		c.1329C>T	p.Gly443Gly	synonymous	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.1329C>T	p.Gly443Gly	synonymous	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367296.8	TSL:5	c.468C>T	p.Gly156Gly	synonymous	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
	NAV1	ENST00000367302.5	TSL:5	c.507C>T	p.Gly169Gly	synonymous	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11949 AN: 152212 Hom.: 524 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0755

GnomAD2 exomes AF: 0.0615 AC: 14948 AN: 242966 AF XY: 0.0612

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0304

Gnomad ASJ exome AF: 0.0914

Gnomad EAS exome AF: 0.000776

Gnomad FIN exome AF: 0.0420

Gnomad NFE exome AF: 0.0777

Gnomad OTH exome AF: 0.0598

GnomAD4 exome AF: 0.0721 AC: 105271 AN: 1459392 Hom.: 4088 Cov.: 59 AF XY: 0.0717 AC XY: 52032 AN XY: 725894

African (AFR) AF: 0.120 AC: 4000 AN: 33458

American (AMR) AF: 0.0326 AC: 1452 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.0967 AC: 2522 AN: 26076

East Asian (EAS) AF: 0.000555 AC: 22 AN: 39654

South Asian (SAS) AF: 0.0519 AC: 4468 AN: 86086

European-Finnish (FIN) AF: 0.0477 AC: 2493 AN: 52246

Middle Eastern (MID) AF: 0.0539 AC: 311 AN: 5766

European-Non Finnish (NFE) AF: 0.0771 AC: 85655 AN: 1111260

Other (OTH) AF: 0.0722 AC: 4348 AN: 60256

GnomAD4 genome AF: 0.0785 AC: 11960 AN: 152330 Hom.: 526 Cov.: 33 AF XY: 0.0737 AC XY: 5491 AN XY: 74478

African (AFR) AF: 0.112 AC: 4677 AN: 41574

American (AMR) AF: 0.0497 AC: 761 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4828

European-Finnish (FIN) AF: 0.0428 AC: 454 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0776 AC: 5281 AN: 68028

Other (OTH) AF: 0.0790 AC: 167 AN: 2114

Alfa AF: 0.0801 Hom.: 184

Bravo AF: 0.0796

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.89
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs1267119; hg19: chr1-201618264;