10-117134320-G-GGCGGCGGCT

Position:

• chr10-117134320-G-GGCGGCGGCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_001112704.2(VAX1):​c.684_692dupAGCCGCCGC​(p.Ala229_Ala231dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000817 in 1,046,902 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (4 hom.)
• Consequence: VAX1 NM_001112704.2 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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 Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001112704.2.
• BP6: Variant 10-117134320-G-GGCGGCGGCT is Benign according to our data. Variant chr10-117134320-G-GGCGGCGGCT is described in ClinVar as [Benign]. Clinvar id is 838114.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAX1	NM_001112704.2	c.684_692dupAGCCGCCGC	p.Ala229_Ala231dup	disruptive_inframe_insertion	3/3	ENST00000369206.6	NP_001106175.1
VAX1	NM_199131.3	c.430-1852_430-1844dupAGCCGCCGC		intron_variant			NP_954582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAX1	ENST00000369206.6	c.684_692dupAGCCGCCGC	p.Ala229_Ala231dup	disruptive_inframe_insertion	3/3	5	NM_001112704.2	ENSP00000358207.4
VAX1	ENST00000277905.6	c.430-1852_430-1844dupAGCCGCCGC		intron_variant		1		ENSP00000277905.2

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 575 AN: 146518 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000106

Gnomad OTH AF: 0.00149

GnomAD4 exome AF: 0.000309 AC: 278 AN: 900278 Hom.: 4 Cov.: 32 AF XY: 0.000266 AC XY: 112 AN XY: 420776

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.000324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000608

Gnomad4 OTH exome AF: 0.000509

GnomAD4 genome AF: 0.00394 AC: 577 AN: 146624 Hom.: 3 Cov.: 32 AF XY: 0.00388 AC XY: 277 AN XY: 71330

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.00135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000106

Gnomad4 OTH AF: 0.00147

Alfa AF: 0.00320 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microphthalmia, syndromic 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1455706624; hg19: chr10-118893831;