10-117134557-GCG-ACA

Variant names:

• chr10-117134557-GCG-ACA
• NM_001112704.2:c.454_456delCGCinsTGT
• VAX1 p.Arg152Cys

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_001112704.2(VAX1):​c.454_456delCGCinsTGT​(p.Arg152Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R152S) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VAX1 NM_001112704.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78
• Publications: 0 publications found

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr10-117134559-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 36954.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.454_456delCGCinsTGT	p.Arg152Cys	missense	N/A	NP_001106175.1	Q5SQQ9-1
	VAX1	NM_199131.3		c.429+1913_429+1915delCGCinsTGT		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.454_456delCGCinsTGT	p.Arg152Cys	missense	N/A	ENSP00000358207.4	Q5SQQ9-1
	VAX1	ENST00000277905.6	TSL:1	c.429+1913_429+1915delCGCinsTGT		intron	N/A	ENSP00000277905.2	Q5SQQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-118894068;