Variant 10-117134094-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001112704.2(VAX1):c.919T>G(p.Ser307Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000826 in 1,538,364 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 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

VAX1
NM_001112704.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25255644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAX1	NM_001112704.2 linkuse as main transcript	c.919T>G	p.Ser307Ala	missense_variant	3/3	ENST00000369206.6
VAX1	NM_199131.3 linkuse as main transcript	c.430-1617T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAX1	ENST00000369206.6 linkuse as main transcript	c.919T>G	p.Ser307Ala	missense_variant	3/3	5	NM_001112704.2	P1	Q5SQQ9-1
VAX1	ENST00000277905.6 linkuse as main transcript	c.430-1617T>G		intron_variant		1			Q5SQQ9-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000489

AC:

AN:

143124

Hom.:

AF XY:

0.0000657

AC XY:

AN XY:

76134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000256

GnomAD4 exome

AF:

0.0000837

AC:

116

AN:

1386234

Hom.:

Cov.:

AF XY:

0.0000819

AC XY:

AN XY:

683450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000298

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:

0.0000987

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000604

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

Jan 03, 2022

The c.919T>G (p.S307A) alteration is located in exon 3 (coding exon 3) of the VAX1 gene. This alteration results from a T to G substitution at nucleotide position 919, causing the serine (S) at amino acid position 307 to be replaced by an alanine (A). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.13

Eigen

Benign

0.11

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.88

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.69

REVEL

Uncertain

0.42

Sift

Benign

0.030

Sift4G

Benign

0.38

Polyphen

0.56

Vest4

0.31

MutPred

0.34

Loss of phosphorylation at S307 (P = 0.0217);

MVP

0.75

MPC

1.1

ClinPred

0.15

GERP RS

4.2

Varity_R

0.29

gMVP

0.57

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