chrX-80022027-T-TACAC

Variant names:

• chrX-80022027-T-TACAC
• rs200577659
• NM_001109878.2:c.-2-203_-2-200dupCACA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001109878.2(TBX22):​c.-2-203_-2-200dupCACA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (614 hom., 2035 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TBX22 NM_001109878.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant X-80022027-T-TACAC is Benign according to our data. Variant chrX-80022027-T-TACAC is described in ClinVar as Benign. ClinVar VariationId is 1297948.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-2-203_-2-200dupCACA		intron	N/A	NP_001103348.1	Q9Y458-1
	TBX22	NM_001109879.2		c.-358-203_-358-200dupCACA		intron	N/A	NP_001103349.1	Q9Y458-2
	TBX22	NM_016954.2		c.-243_-242insACAC		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.-2-241_-2-240insACAC		intron	N/A	ENSP00000362393.3	Q9Y458-1
	TBX22	ENST00000968708.1		c.-3+153_-3+154insACAC		intron	N/A	ENSP00000638767.1
	TBX22	ENST00000476373.1	TSL:3	n.120-241_120-240insACAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 10608 AN: 92820 Hom.: 615 Cov.: 0

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0878

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0505

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.147

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.114 AC: 10611 AN: 92838 Hom.: 614 Cov.: 0 AF XY: 0.101 AC XY: 2035 AN XY: 20054

African (AFR) AF: 0.102 AC: 2650 AN: 25882

American (AMR) AF: 0.274 AC: 2321 AN: 8485

Ashkenazi Jewish (ASJ) AF: 0.0892 AC: 203 AN: 2276

East Asian (EAS) AF: 0.147 AC: 434 AN: 2956

South Asian (SAS) AF: 0.0738 AC: 134 AN: 1816

European-Finnish (FIN) AF: 0.0702 AC: 277 AN: 3948

Middle Eastern (MID) AF: 0.0393 AC: 7 AN: 178

European-Non Finnish (NFE) AF: 0.0956 AC: 4348 AN: 45459

Other (OTH) AF: 0.148 AC: 186 AN: 1257

Alfa AF: 0.0541 Hom.: 192

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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;