NM_012476.3:c.131C>T

Variant names:

• chr2-70900752-C-T
• rs966757865
• NM_012476.3:c.131C>T

Variant summary

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

The NM_012476.3(VAX2):​c.131C>T​(p.Thr44Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,329,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: VAX2 NM_012476.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

VAX2 (HGNC:12661): (ventral anterior homeobox 2) This gene encodes a homeobox protein and is almost exclusively expressed in the ventral portion of the retina during development. In mouse studies, this gene was found to be required for the correct formation of the optic fissure and other aspects of retinal development. [provided by RefSeq, Sep 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=0.15639538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAX2	NM_012476.3	c.131C>T	p.Thr44Met	missense_variant	Exon 1 of 3	ENST00000234392.3	NP_036608.1
VAX2	XM_011532750.4	c.131C>T	p.Thr44Met	missense_variant	Exon 1 of 4		XP_011531052.1
VAX2	XM_011532751.4	c.131C>T	p.Thr44Met	missense_variant	Exon 1 of 4		XP_011531053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAX2	ENST00000234392.3	c.131C>T	p.Thr44Met	missense_variant	Exon 1 of 3	1	NM_012476.3	ENSP00000234392.2
VAX2	ENST00000432367.6	n.-47C>T		upstream_gene_variant		5		ENSP00000405114.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1329612 Hom.: 0 Cov.: 33 AF XY: 0.00000153 AC XY: 1 AN XY: 655042

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: 0.00000191

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000409 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.97
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.13
Sift	Benign	0.060	T
Sift4G	Benign	0.11	T
Polyphen		0.47	P
Vest4		0.11
MutPred		0.18		Loss of glycosylation at T44 (P = 0.0112);
MVP		0.90
MPC		0.057
ClinPred		0.45	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs966757865; hg19: chr2-71127882;