10-117134335-G-A

Position:

• chr10-117134335-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001112704.2(VAX1):​c.678C>T​(p.Ala226Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,052,500 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (3 hom.)
• Consequence: VAX1 NM_001112704.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.24

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-117134335-G-A is Benign according to our data. Variant chr10-117134335-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 707045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAX1	NM_001112704.2	c.678C>T	p.Ala226Ala	synonymous_variant	3/3	ENST00000369206.6	NP_001106175.1
VAX1	NM_199131.3	c.430-1858C>T		intron_variant			NP_954582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAX1	ENST00000369206.6	c.678C>T	p.Ala226Ala	synonymous_variant	3/3	5	NM_001112704.2	ENSP00000358207.4
VAX1	ENST00000277905.6	c.430-1858C>T		intron_variant		1		ENSP00000277905.2

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 154 AN: 146638 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00108

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00158

Gnomad OTH AF: 0.000494

GnomAD3 exomes AF: 0.00174 AC: 1 AN: 574 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 348

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad NFE exome AF: 0.00182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00201 AC: 1820 AN: 905754 Hom.: 3 Cov.: 32 AF XY: 0.00192 AC XY: 815 AN XY: 423666

Gnomad4 AFR exome AF: 0.000574

Gnomad4 AMR exome AF: 0.00223

Gnomad4 ASJ exome AF: 0.000687

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.000245

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00105 AC: 154 AN: 146746 Hom.: 0 Cov.: 32 AF XY: 0.000910 AC XY: 65 AN XY: 71404

Gnomad4 AFR AF: 0.000415

Gnomad4 AMR AF: 0.00108

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00158

Gnomad4 OTH AF: 0.000489

Alfa AF: 0.00164 Hom.: 0

Bravo AF: 0.00105

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Microphthalmia, syndromic 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2023

- -

VAX1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 14, 2023

This variant is classified as likely 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	-0.53
CADD	Benign	7.4
DANN	Benign	0.89

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: rs534482978; hg19: chr10-118893846;