NM_001109878.2:c.-2-211_-2-200delCACACACACACA

Variant names:

• chrX-80022027-TACACACACACAC-T
• rs200577659
• NM_001109878.2:c.-2-211_-2-200delCACACACACACA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001109878.2(TBX22):​c.-2-211_-2-200delCACACACACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00044 (0 hom., 7 hem., cov: 0)
• Consequence: TBX22 NM_001109878.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 1 publications found

Genes affected

TBX22 (HGNC:11600): (T-box transcription factor 22) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Mutations in this gene have been associated with the inherited X-linked disorder, Cleft palate with ankyloglossia, and it is believed to play a major role in human palatogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TBX22 Gene-Disease associations (from GenCC):

• cleft palate with or without ankyloglossia, X-linked

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Abruzzo-Erickson syndrome

  Inheritance: XL Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

ENSG00000300464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000441 (41/92964) while in subpopulation AFR AF = 0.00081 (21/25920). AF 95% confidence interval is 0.000542. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 7 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109878.2. 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
	TBX22	NM_001109878.2	MANE Select	c.-2-211_-2-200delCACACACACACA		intron	N/A	NP_001103348.1	Q9Y458-1
	TBX22	NM_001109879.2		c.-358-211_-358-200delCACACACACACA		intron	N/A	NP_001103349.1	Q9Y458-2
	TBX22	NM_016954.2		c.-242_-231delACACACACACAC		upstream_gene	N/A	NP_058650.1	Q9Y458-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX22	ENST00000373296.8	TSL:5 MANE Select	c.-2-240_-2-229delACACACACACAC		intron	N/A	ENSP00000362393.3	Q9Y458-1
	TBX22	ENST00000968708.1		c.-3+154_-3+165delACACACACACAC		intron	N/A	ENSP00000638767.1
	TBX22	ENST00000476373.1	TSL:3	n.120-240_120-229delACACACACACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000430 AC: 40 AN: 92946 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000337

Gnomad SAS AF: 0.000547

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000374

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000441 AC: 41 AN: 92964 Hom.: 0 Cov.: 0 AF XY: 0.000348 AC XY: 7 AN XY: 20098

African (AFR) AF: 0.000810 AC: 21 AN: 25920

American (AMR) AF: 0.000118 AC: 1 AN: 8507

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2279

East Asian (EAS) AF: 0.000338 AC: 1 AN: 2961

South Asian (SAS) AF: 0.000551 AC: 1 AN: 1814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3963

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.000374 AC: 17 AN: 45504

Other (OTH) AF: 0.00 AC: 0 AN: 1258

Alfa AF: 0.00 Hom.: 192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.75

Splicing

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

Other links and lift over

dbSNP: rs200577659; hg19: chrX-79277526;