Genetic Variant VAX1:p.Ala230Ser (chr10-117134325-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001112704.2(VAX1):c.688G>T(p.Ala230Ser) 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. 15/22 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. A230T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VAX1
NM_001112704.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

microphthalmia, syndromic 11
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

VAX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26646265).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112704.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX1	NM_001112704.2	MANE Select	c.688G>T	p.Ala230Ser	missense	Exon 3 of 3	NP_001106175.1	Q5SQQ9-1
	VAX1	NM_199131.3		c.430-1848G>T		intron	N/A	NP_954582.1	Q5SQQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX1	ENST00000369206.6	TSL:5 MANE Select	c.688G>T	p.Ala230Ser	missense	Exon 3 of 3	ENSP00000358207.4	Q5SQQ9-1
	VAX1	ENST00000277905.6	TSL:1	c.430-1848G>T		intron	N/A	ENSP00000277905.2	Q5SQQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

884056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

412588

African (AFR)

AF:

0.00

AC:

AN:

16940

American (AMR)

AF:

0.00

AC:

AN:

2626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6538

East Asian (EAS)

AF:

0.00

AC:

AN:

6302

South Asian (SAS)

AF:

0.00

AC:

AN:

17776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1884

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

795746

Other (OTH)

AF:

0.00

AC:

AN:

30432

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

1.2

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.38

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.46

PhyloP100

0.035

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.49

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

0.59

Polyphen

0.0030

Vest4

0.21

MutPred

0.43

Gain of glycosylation at A230 (P = 6e-04)

MVP

0.71

MPC

1.2

ClinPred

0.039

GERP RS

-1.4

Varity_R

0.043

gMVP

0.29

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over