chr1-201648756-G-A

Variant names:

• chr1-201648756-G-A
• NM_001389617.1:c.949G>A

Variant summary

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

The NM_001389617.1(NAV1):​c.949G>A​(p.Ala317Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,249,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. A317S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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=0.1224629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.949G>A	p.Ala317Thr	missense_variant	Exon 5 of 34	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.949G>A	p.Ala317Thr	missense_variant	Exon 4 of 32		NP_001376545.1
NAV1	NM_001389615.1	c.949G>A	p.Ala317Thr	missense_variant	Exon 5 of 31		NP_001376544.1
NAV1	NM_020443.5	c.88G>A	p.Ala30Thr	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.949G>A	p.Ala317Thr	missense_variant	Exon 5 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.88G>A	p.Ala30Thr	missense_variant	Exon 1 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.127G>A	p.Ala43Thr	missense_variant	Exon 3 of 30	5		ENSP00000356271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1249990 Hom.: 0 Cov.: 53 AF XY: 0.00 AC XY: 0 AN XY: 611630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000608

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: 0.00

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	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.62	T;T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.070
Sift	Benign	0.080	T;T
Sift4G	Benign	0.57	T;T
Vest4		0.084
MutPred		0.13		.;Gain of phosphorylation at A30 (P = 0.0026);
MVP		0.28
MPC		0.94
ClinPred		0.11	T
GERP RS		2.5
Varity_R		0.053
gMVP		0.15

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: chr1-201617884;