10-117134325-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001112704.2(VAX1):c.688G>A(p.Ala230Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,030,702 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (19 hom.)
• Consequence: VAX1 NM_001112704.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008133799).
• BP6: Variant 10-117134325-C-T is Benign according to our data. Variant chr10-117134325-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 707040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1747/146648) while in subpopulation AFR AF= 0.0406 (1661/40942). AF 95% confidence interval is 0.0389. There are 27 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAX1	NM_001112704.2	c.688G>A	p.Ala230Thr	missense_variant	3/3	ENST00000369206.6
VAX1	NM_199131.3	c.430-1848G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAX1	ENST00000369206.6	c.688G>A	p.Ala230Thr	missense_variant	3/3	5	NM_001112704.2	P1
VAX1	ENST00000277905.6	c.430-1848G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1741 AN: 146540 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000136

Gnomad OTH AF: 0.0104

GnomAD4 exome AF: 0.00119 AC: 1050 AN: 884054 Hom.: 19 Cov.: 32 AF XY: 0.00111 AC XY: 457 AN XY: 412586

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.00457

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000563

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.00299

GnomAD4 genome AF: 0.0119 AC: 1747 AN: 146648 Hom.: 27 Cov.: 32 AF XY: 0.0118 AC XY: 842 AN XY: 71364

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.00365

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000136

Gnomad4 OTH AF: 0.0103

Alfa AF: 0.000706 Hom.: 0

Bravo AF: 0.0132

ExAC AF: 0.00291 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microphthalmia, syndromic 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	12
Dann	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.040	N
REVEL	Benign	0.20
Sift	Benign	0.29	T
Sift4G	Benign	0.13	T
Polyphen		0.0040	B
Vest4		0.27
MVP		0.70
MPC		1.4
ClinPred		0.17	T
GERP RS		-1.4
Varity_R		0.045
gMVP		0.37

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: rs571879048; hg19: chr10-118893836;