1-201648817-CCGGCGG-CCGGCGGCGG

Variant names:

• chr1-201648817-C-CCGG
• rs561927033
• NM_001389617.1:c.1024_1026dupGGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001389617.1(NAV1):​c.1024_1026dupGGC​(p.Gly342dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,582,236 control chromosomes in the GnomAD database, including 351 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (23 hom., cov: 32)
  • Exomes 𝑓: 0.019 (328 hom.)
• Consequence: NAV1 NM_001389617.1 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 1 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 -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001389617.1
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0126 (1910/151972) while in subpopulation NFE AF = 0.0214 (1454/67908). AF 95% confidence interval is 0.0205. There are 23 homozygotes in GnomAd4. There are 901 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1910 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.1024_1026dupGGC	p.Gly342dup	conservative_inframe_insertion	Exon 5 of 34	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.1024_1026dupGGC	p.Gly342dup	conservative_inframe_insertion	Exon 4 of 32	NP_001376545.1
	NAV1	NM_001389615.1		c.1024_1026dupGGC	p.Gly342dup	conservative_inframe_insertion	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.1024_1026dupGGC	p.Gly342dup	conservative_inframe_insertion	Exon 5 of 34	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367296.8	TSL:5	c.163_165dupGGC	p.Gly55dup	conservative_inframe_insertion	Exon 1 of 30	ENSP00000356265.4	Q8NEY1-1
	NAV1	ENST00000367302.5	TSL:5	c.202_204dupGGC	p.Gly68dup	conservative_inframe_insertion	Exon 3 of 30	ENSP00000356271.1	A0A0A0MRJ3

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1911 AN: 151858 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00774

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0121 AC: 2160 AN: 178836 AF XY: 0.0119

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.00787

Gnomad ASJ exome AF: 0.00650

Gnomad EAS exome AF: 0.000144

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0207

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0194 AC: 27677 AN: 1430264 Hom.: 328 Cov.: 54 AF XY: 0.0186 AC XY: 13219 AN XY: 709352

African (AFR) AF: 0.00316 AC: 103 AN: 32636

American (AMR) AF: 0.00751 AC: 301 AN: 40100

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 181 AN: 25156

East Asian (EAS) AF: 0.000129 AC: 5 AN: 38828

South Asian (SAS) AF: 0.000995 AC: 83 AN: 83398

European-Finnish (FIN) AF: 0.0113 AC: 529 AN: 46722

Middle Eastern (MID) AF: 0.00621 AC: 35 AN: 5638

European-Non Finnish (NFE) AF: 0.0233 AC: 25577 AN: 1098766

Other (OTH) AF: 0.0146 AC: 863 AN: 59020

GnomAD4 genome AF: 0.0126 AC: 1910 AN: 151972 Hom.: 23 Cov.: 32 AF XY: 0.0121 AC XY: 901 AN XY: 74294

African (AFR) AF: 0.00349 AC: 145 AN: 41492

American (AMR) AF: 0.00773 AC: 118 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0137 AC: 144 AN: 10530

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0214 AC: 1454 AN: 67908

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.00566 Hom.: 2

Bravo AF: 0.0123

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3
Mutation Taster		=83/17	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs561927033; hg19: chr1-201617945; COSMIC: COSV99819532;