rs554140675

chr10-117134371-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001112704.2(VAX1):c.642G>A(p.Leu214=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,211,662 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0010 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: VAX1 NM_001112704.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -3.17

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 10-117134371-C-T is Benign according to our data. Variant chr10-117134371-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 283191.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAX1	NM_001112704.2	c.642G>A	p.Leu214=	synonymous_variant	3/3	ENST00000369206.6
VAX1	NM_199131.3	c.430-1894G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAX1	ENST00000369206.6	c.642G>A	p.Leu214=	synonymous_variant	3/3	5	NM_001112704.2	P1
VAX1	ENST00000277905.6	c.430-1894G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 154 AN: 148374 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000439

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00429

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00296

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000793

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000969 AC: 3 AN: 3096 Hom.: 0 AF XY: 0.000475 AC XY: 1 AN XY: 2106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00143

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000585

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00115 AC: 1226 AN: 1063180 Hom.: 2 Cov.: 32 AF XY: 0.00111 AC XY: 558 AN XY: 504508

Gnomad4 AFR exome AF: 0.000185

Gnomad4 AMR exome AF: 0.00366

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00223

Gnomad4 SAS exome AF: 0.000543

Gnomad4 FIN exome AF: 0.0000963

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.00168

GnomAD4 genome AF: 0.00103 AC: 153 AN: 148482 Hom.: 2 Cov.: 32 AF XY: 0.000995 AC XY: 72 AN XY: 72396

Gnomad4 AFR AF: 0.000438

Gnomad4 AMR AF: 0.00422

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00297

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000793

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000900 Hom.: 0

Bravo AF: 0.00162

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 22, 2015

- -

VAX1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

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). -

Microphthalmia, syndromic 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	2.1
Dann	Benign	0.90

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: rs554140675; hg19: chr10-118893882;