10-117134068-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001112704.2(VAX1):c.945C>T(p.Ala315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000507 in 1,535,468 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (6 hom.)
• Consequence: VAX1 NM_001112704.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.59

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-117134068-G-A is Benign according to our data. Variant chr10-117134068-G-A is described in ClinVar as [Benign]. Clinvar id is 2780824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAX1	NM_001112704.2	c.945C>T	p.Ala315=	synonymous_variant	3/3	ENST00000369206.6
VAX1	NM_199131.3	c.430-1591C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAX1	ENST00000369206.6	c.945C>T	p.Ala315=	synonymous_variant	3/3	5	NM_001112704.2	P1
VAX1	ENST00000277905.6	c.430-1591C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000927 AC: 141 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00123 AC: 173 AN: 140144 Hom.: 2 AF XY: 0.00118 AC XY: 88 AN XY: 74606

Gnomad AFR exome AF: 0.000950

Gnomad AMR exome AF: 0.0000945

Gnomad ASJ exome AF: 0.0181

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000218

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.000461 AC: 638 AN: 1383298 Hom.: 6 Cov.: 32 AF XY: 0.000468 AC XY: 319 AN XY: 682010

Gnomad4 AFR exome AF: 0.00142

Gnomad4 AMR exome AF: 0.0000906

Gnomad4 ASJ exome AF: 0.0168

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000970

Gnomad4 OTH exome AF: 0.00122

GnomAD4 genome AF: 0.000927 AC: 141 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.000928 AC XY: 69 AN XY: 74338

Gnomad4 AFR AF: 0.00150

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00167 Hom.: 3

Bravo AF: 0.000967

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Microphthalmia, syndromic 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 24, 2023

- -

VAX1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	14
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs201441554; hg19: chr10-118893579;