10-117133720-A-G

Position:

• chr10-117133720-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001112704.2(VAX1):​c.*288T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,145,050 control chromosomes in the GnomAD database, including 364,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (37642 hom., cov: 32)
  • Exomes 𝑓: 0.81 (326436 hom.)
• Consequence: VAX1 NM_001112704.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-117133720-A-G is Benign according to our data. Variant chr10-117133720-A-G is described in ClinVar as [Benign]. Clinvar id is 1285816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAX1	NM_001112704.2	c.*288T>C		3_prime_UTR_variant	3/3	ENST00000369206.6	NP_001106175.1
VAX1	NM_199131.3	c.430-1243T>C		intron_variant			NP_954582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAX1	ENST00000369206	c.*288T>C		3_prime_UTR_variant	3/3	5	NM_001112704.2	ENSP00000358207.4
VAX1	ENST00000277905.6	c.430-1243T>C		intron_variant		1		ENSP00000277905.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103131 AN: 151972 Hom.: 37630 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.710

GnomAD4 exome AF: 0.807 AC: 800880 AN: 992960 Hom.: 326436 Cov.: 61 AF XY: 0.807 AC XY: 377749 AN XY: 467924

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.791

Gnomad4 FIN exome AF: 0.805

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.779

GnomAD4 genome AF: 0.678 AC: 103163 AN: 152090 Hom.: 37642 Cov.: 32 AF XY: 0.680 AC XY: 50540 AN XY: 74344

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.709

Alfa AF: 0.788 Hom.: 44999

Bravo AF: 0.650

Asia WGS AF: 0.598 AC: 2082 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.8
DANN	Benign	0.43

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: rs6585429; hg19: chr10-118893231;