Variant 10-117134312-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001112704.2(VAX1):c.701C>T(p.Pro234Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000339 in 1,090,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

VAX1
NM_001112704.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

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:

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ACMG classification

Classification made for transcript

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=0.36207616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAX1	NM_001112704.2 linkuse as main transcript	c.701C>T	p.Pro234Leu	missense_variant	3/3	ENST00000369206.6	NP_001106175.1	Q5SQQ9-1
VAX1	NM_199131.3 linkuse as main transcript	c.430-1835C>T		intron_variant			NP_954582.1	Q5SQQ9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAX1	ENST00000369206.6 linkuse as main transcript	c.701C>T	p.Pro234Leu	missense_variant	3/3	5	NM_001112704.2	ENSP00000358207.4		Q5SQQ9-1
VAX1	ENST00000277905.6 linkuse as main transcript	c.430-1835C>T		intron_variant		1		ENSP00000277905.2		Q5SQQ9-2

Frequencies

GnomAD3 genomes

AF:

0.00000681

AC:

AN:

146948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000382

AC:

AN:

943432

Hom.:

Cov.:

AF XY:

0.0000384

AC XY:

AN XY:

442496

show subpopulations

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:

0.0000360

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

AF:

0.00000681

AC:

AN:

146948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2024

The c.701C>T (p.P234L) alteration is located in exon 3 (coding exon 3) of the VAX1 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the proline (P) at amino acid position 234 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.043

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.049

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.99

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Benign

0.097

Polyphen

0.72

Vest4

0.20

MutPred

0.33

Loss of relative solvent accessibility (P = 0.0071);

MVP

0.52

MPC

1.0

ClinPred

0.73

GERP RS

4.2

Varity_R

0.18

gMVP

0.28

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