Genetic Variant NM_001112704.2:c.730C>T (chr10-117134283-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001112704.2(VAX1):c.730C>T(p.Pro244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,079,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

VAX1
NM_001112704.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24154112).

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.730C>T	p.Pro244Ser	missense	Exon 3 of 3	NP_001106175.1	Q5SQQ9-1
	VAX1	NM_199131.3		c.430-1806C>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.730C>T	p.Pro244Ser	missense	Exon 3 of 3	ENSP00000358207.4	Q5SQQ9-1
	VAX1	ENST00000277905.6	TSL:1	c.430-1806C>T		intron	N/A	ENSP00000277905.2	Q5SQQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.27e-7

AC:

AN:

1079324

Hom.:

Cov.:

AF XY:

0.00000195

AC XY:

AN XY:

512086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22130

American (AMR)

AF:

0.00

AC:

AN:

7706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13676

East Asian (EAS)

AF:

0.0000398

AC:

AN:

25134

South Asian (SAS)

AF:

0.00

AC:

AN:

23020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2864

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920108

Other (OTH)

AF:

0.00

AC:

AN:

42800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

0.0070

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.015

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.55

PhyloP100

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.63

REVEL

Benign

0.26

Sift

Benign

0.67

Sift4G

Benign

0.59

Polyphen

0.42

Vest4

0.24

MutPred

0.30

Loss of catalytic residue at P244 (P = 0.0031)

MVP

0.58

MPC

0.94

ClinPred

0.24

GERP RS

4.2

Varity_R

0.098

gMVP

0.58

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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