10-117134298-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001112704.2(VAX1):c.715G>T(p.Ala239Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,170,924 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. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000088 ( 0 hom., cov: 32)

Exomes 𝑓: 9.8e-7 ( 0 hom. )

Consequence

VAX1
NM_001112704.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0870

Variant links:

Genes affected

VAX1 (HGNC:12660): (ventral anterior homeobox 1) This gene encodes a homeo-domain containing protein from a class of homeobox transcription factors which are conserved in vertebrates. Genes of this family are involved in the regulation of body development and morphogenesis. The most conserved genes, called HOX genes are found in special gene clusters. This gene belongs to the VAX subfamily and lies in the vicinity of the EMX homeobox gene family. Another member of VAX family is located on chromosome 2. The encoded protein may play an important role in the development of anterior ventral forebrain and visual system. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

VAX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15385842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAX1	NM_001112704.2 linkuse as main transcript	c.715G>T	p.Ala239Ser	missense_variant	3/3	ENST00000369206.6
VAX1	NM_199131.3 linkuse as main transcript	c.430-1821G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAX1	ENST00000369206.6 linkuse as main transcript	c.715G>T	p.Ala239Ser	missense_variant	3/3	5	NM_001112704.2	P1	Q5SQQ9-1
VAX1	ENST00000277905.6 linkuse as main transcript	c.430-1821G>T		intron_variant		1			Q5SQQ9-2

Frequencies

GnomAD3 genomes

AF:

0.0000883

AC:

AN:

147144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.77e-7

AC:

AN:

1023780

Hom.:

Cov.:

AF XY:

0.00000207

AC XY:

AN XY:

482656

show subpopulations

Gnomad4 AFR exome

AF:

0.0000479

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000883

AC:

AN:

147144

Hom.:

Cov.:

AF XY:

0.0000838

AC XY:

AN XY:

71602

show subpopulations

Gnomad4 AFR

AF:

0.000294

Gnomad4 AMR

AF:

0.0000674

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.715G>T (p.A239S) alteration is located in exon 3 (coding exon 3) of the VAX1 gene. This alteration results from a G to T substitution at nucleotide position 715, causing the alanine (A) at amino acid position 239 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 04, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

Cadd

Benign

6.3

Dann

Uncertain

0.98

DEOGEN2

Benign

0.097

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.42

REVEL

Benign

0.21

Sift

Benign

0.25

Sift4G

Benign

0.90

Polyphen

0.10

Vest4

0.10

MutPred

0.24

Gain of glycosylation at A239 (P = 3e-04);

MVP

0.60

MPC

1.5

ClinPred

0.11

GERP RS

0.97

Varity_R

0.057

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over