1-201648808-C-T

Variant names:

• chr1-201648808-C-T
• NM_001389617.1:c.1001C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001389617.1(NAV1):​c.1001C>T​(p.Ala334Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,411,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A334G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16544539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.1001C>T	p.Ala334Val	missense_variant	Exon 5 of 34	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.1001C>T	p.Ala334Val	missense_variant	Exon 4 of 32		NP_001376545.1
NAV1	NM_001389615.1	c.1001C>T	p.Ala334Val	missense_variant	Exon 5 of 31		NP_001376544.1
NAV1	NM_020443.5	c.140C>T	p.Ala47Val	missense_variant	Exon 1 of 30		NP_065176.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.1001C>T	p.Ala334Val	missense_variant	Exon 5 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.140C>T	p.Ala47Val	missense_variant	Exon 1 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.179C>T	p.Ala60Val	missense_variant	Exon 3 of 30	5		ENSP00000356271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411542 Hom.: 0 Cov.: 54 AF XY: 0.00 AC XY: 0 AN XY: 698540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.048
Sift	Benign	0.13	T;T
Sift4G	Benign	0.34	T;T
Vest4		0.25
MutPred		0.22		.;Gain of sheet (P = 0.0125);
MVP		0.16
MPC		1.7
ClinPred		0.74	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-201617936;