NM_001024383.2:c.637A>T

Variant names:

• chr12-77968668-A-T
• NM_001024383.2:c.637A>T

Variant summary

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

The NM_001024383.2(NAV3):​c.637A>T​(p.Ser213Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAV3 NM_001024383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1580883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV3	NM_001024383.2	c.637A>T	p.Ser213Cys	missense_variant	Exon 5 of 40	ENST00000397909.7	NP_001019554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV3	ENST00000397909.7	c.637A>T	p.Ser213Cys	missense_variant	Exon 5 of 40	1	NM_001024383.2	ENSP00000381007.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.013	T;T;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.87
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	.;.;L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.80	.;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.069	.;T;T;T
Sift4G	Benign	0.096	.;T;D;D
Polyphen		0.92, 0.84	.;.;P;P
Vest4		0.56, 0.51
MutPred		0.34		.;Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.18
MPC		0.33
ClinPred		0.38	T
GERP RS		-0.67
Varity_R		0.072
gMVP		0.34

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: chr12-78362448;