NM_145117.5:c.155A>C

Variant names:

• chr11-19713850-A-C
• NM_145117.5:c.155A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145117.5(NAV2):​c.155A>C​(p.Tyr52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. Y52C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAV2 NM_145117.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20

Genes affected

NAV2 (HGNC:15997): (neuron navigator 2) This gene encodes a member of the neuron navigator gene family, which may play a role in cellular growth and migration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

LEISA1 (HGNC:55264): (lncRNA enhancing IL-6/STAT3 signaling activation 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3114677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV2	NM_145117.5	c.155A>C	p.Tyr52Ser	missense_variant	Exon 1 of 38	ENST00000349880.9	NP_660093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV2	ENST00000349880.9	c.155A>C	p.Tyr52Ser	missense_variant	Exon 1 of 38	1	NM_145117.5	ENSP00000309577.6
NAV2	ENST00000360655.8	c.76-118634A>C		intron_variant	Intron 1 of 37	1		ENSP00000353871.4
NAV2	ENST00000396087.7	c.155A>C	p.Tyr52Ser	missense_variant	Exon 1 of 41	5		ENSP00000379396.3
NAV2	ENST00000396085.6	c.155A>C	p.Tyr52Ser	missense_variant	Exon 1 of 39	5		ENSP00000379394.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461290 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726940

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	.;.;T;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T;T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.49	N;.;.;N;N
REVEL	Benign	0.26
Sift	Benign	0.031	D;.;.;D;D
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.95	.;.;.;P;.
Vest4		0.61
MutPred		0.27		Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);Loss of catalytic residue at Y52 (P = 0.0363);
MVP		0.043
MPC		0.79
ClinPred		0.68	D
GERP RS		2.9
Varity_R		0.11
gMVP		0.62

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: chr11-19735396;