NM_001389617.1:c.918C>A

Variant names:

• chr1-201648725-C-A
• rs571656889
• NM_001389617.1:c.918C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001389617.1(NAV1):​c.918C>A​(p.Gly306Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,414,162 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (8 hom.)
• Consequence: NAV1 NM_001389617.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.839
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 1-201648725-C-A is Benign according to our data. Variant chr1-201648725-C-A is described in ClinVar as Benign. ClinVar VariationId is 767742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.839 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00701 (1066/152122) while in subpopulation AFR AF = 0.0233 (968/41518). AF 95% confidence interval is 0.0221. There are 16 homozygotes in GnomAd4. There are 498 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1066 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.918C>A	p.Gly306Gly	synonymous	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.918C>A	p.Gly306Gly	synonymous	Exon 4 of 32	NP_001376545.1
	NAV1	NM_001389615.1		c.918C>A	p.Gly306Gly	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.918C>A	p.Gly306Gly	synonymous	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367296.8	TSL:5	c.57C>A	p.Gly19Gly	synonymous	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
	NAV1	ENST00000367302.5	TSL:5	c.96C>A	p.Gly32Gly	synonymous	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1053 AN: 152014 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.000851 AC: 44 AN: 51688 AF XY: 0.000818

Gnomad AFR exome AF: 0.0273

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000463

Gnomad OTH exome AF: 0.000697

GnomAD4 exome AF: 0.000797 AC: 1006 AN: 1262040 Hom.: 8 Cov.: 54 AF XY: 0.000758 AC XY: 469 AN XY: 619042

African (AFR) AF: 0.0225 AC: 576 AN: 25636

American (AMR) AF: 0.00241 AC: 46 AN: 19068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20956

East Asian (EAS) AF: 0.00 AC: 0 AN: 27732

South Asian (SAS) AF: 0.000118 AC: 7 AN: 59446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32600

Middle Eastern (MID) AF: 0.00292 AC: 12 AN: 4106

European-Non Finnish (NFE) AF: 0.000240 AC: 245 AN: 1020486

Other (OTH) AF: 0.00231 AC: 120 AN: 52010

GnomAD4 genome AF: 0.00701 AC: 1066 AN: 152122 Hom.: 16 Cov.: 32 AF XY: 0.00670 AC XY: 498 AN XY: 74358

African (AFR) AF: 0.0233 AC: 968 AN: 41518

American (AMR) AF: 0.00353 AC: 54 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67968

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.00801

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	-0.25
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		0.84
PromoterAI		-0.054	Neutral
Mutation Taster		=100/0	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: rs571656889; hg19: chr1-201617853;