rs1243631591

Variant names:

• chr12-77831538-T-A
• NM_001024383.2:c.77T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-77831538-T-A
• chr12-77831538-T-C
• chr12-77831538-T-G

Variant summary

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

The NM_001024383.2(NAV3):​c.77T>A​(p.Ile26Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NAV3 NM_001024383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

Genes affected

NAV3 (HGNC:15998): (neuron navigator 3) 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. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.77T>A	p.Ile26Lys	missense_variant	Exon 1 of 40	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.77T>A	p.Ile26Lys	missense_variant	Exon 1 of 40	1	NM_001024383.2	ENSP00000381007.2
NAV3	ENST00000536525.6	c.77T>A	p.Ile26Lys	missense_variant	Exon 1 of 39	1		ENSP00000446132.2
NAV3	ENST00000549464.5	c.77T>A	p.Ile26Lys	missense_variant	Exon 1 of 10	5		ENSP00000446628.1
NAV3	ENST00000550042.2	c.73-108781T>A		intron_variant	Intron 2 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727206

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: 0.00000180

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	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.059	T;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;T;T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.5	.;L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0, 0.99	.;D;D
Vest4		0.57, 0.60
MutPred		0.42		Gain of ubiquitination at I26 (P = 0.0069);Gain of ubiquitination at I26 (P = 0.0069);Gain of ubiquitination at I26 (P = 0.0069);
MVP		0.62
MPC		0.41
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.30
gMVP		0.64

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: chr12-78225318; COSMIC: COSV57090907;