NM_001112704.2:c.939C>T

Variant names:

• chr10-117134074-G-A
• rs1589946008
• NM_001112704.2:c.939C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001112704.2(VAX1):​c.939C>T​(p.Ser313Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: VAX1 NM_001112704.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.175
• Publications: 0 publications found

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]

VAX1 Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 11

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-117134074-G-A is Benign according to our data. Variant chr10-117134074-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 733123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.175 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112704.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX1	NM_001112704.2	MANE Select	c.939C>T	p.Ser313Ser	synonymous	Exon 3 of 3	NP_001106175.1	Q5SQQ9-1
	VAX1	NM_199131.3		c.430-1597C>T		intron	N/A	NP_954582.1	Q5SQQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAX1	ENST00000369206.6	TSL:5 MANE Select	c.939C>T	p.Ser313Ser	synonymous	Exon 3 of 3	ENSP00000358207.4	Q5SQQ9-1
	VAX1	ENST00000277905.6	TSL:1	c.430-1597C>T		intron	N/A	ENSP00000277905.2	Q5SQQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1383812 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 682282

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30258

American (AMR) AF: 0.00 AC: 0 AN: 33296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24842

East Asian (EAS) AF: 0.00 AC: 0 AN: 33990

South Asian (SAS) AF: 0.00 AC: 0 AN: 76894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1072348

Other (OTH) AF: 0.00 AC: 0 AN: 57376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0662318), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs1589946008; hg19: chr10-118893585;