X-80022128-GGTTTTGTTTT-GGTTTT

Variant names:

• chrX-80022128-GGTTTT-G
• rs3048712
• NM_001109878.2:c.-2-119_-2-115delGTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001109878.2(TBX22):​c.-2-119_-2-115delGTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 551,747 control chromosomes in the GnomAD database, including 29,487 homozygotes. There are 67,005 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (5222 hom., 9607 hem., cov: 6)
  • Exomes 𝑓: 0.38 (24265 hom. 57398 hem.)
• Consequence: TBX22 NM_001109878.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.467
• Publications: 2 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 -10 ACMG points.

• BP6: Variant X-80022128-GGTTTT-G is Benign according to our data. Variant chrX-80022128-GGTTTT-G is described in ClinVar as Benign. ClinVar VariationId is 1271765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

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.-2-119_-2-115delGTTTT		intron	N/A	NP_001103348.1	Q9Y458-1
	TBX22	NM_001109879.2		c.-358-119_-358-115delGTTTT		intron	N/A	NP_001103349.1	Q9Y458-2
	TBX22	NM_016954.2		c.-141_-137delGTTTT		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.-2-139_-2-135delGTTTT		intron	N/A	ENSP00000362393.3	Q9Y458-1
	TBX22	ENST00000968708.1		c.-2-139_-2-135delGTTTT		intron	N/A	ENSP00000638767.1
	TBX22	ENST00000476373.1	TSL:3	n.120-139_120-135delGTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.352 AC: 37490 AN: 106541 Hom.: 5224 Cov.: 6

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.384 AC: 170963 AN: 445162 Hom.: 24265 AF XY: 0.413 AC XY: 57398 AN XY: 138838

African (AFR) AF: 0.285 AC: 3357 AN: 11792

American (AMR) AF: 0.393 AC: 6632 AN: 16865

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 4663 AN: 11904

East Asian (EAS) AF: 0.686 AC: 16353 AN: 23834

South Asian (SAS) AF: 0.602 AC: 19083 AN: 31691

European-Finnish (FIN) AF: 0.490 AC: 16687 AN: 34083

Middle Eastern (MID) AF: 0.441 AC: 841 AN: 1908

European-Non Finnish (NFE) AF: 0.325 AC: 94256 AN: 289613

Other (OTH) AF: 0.387 AC: 9091 AN: 23472

GnomAD4 genome AF: 0.352 AC: 37489 AN: 106585 Hom.: 5222 Cov.: 6 AF XY: 0.326 AC XY: 9607 AN XY: 29433

African (AFR) AF: 0.285 AC: 8361 AN: 29345

American (AMR) AF: 0.372 AC: 3674 AN: 9874

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1020 AN: 2575

East Asian (EAS) AF: 0.625 AC: 2029 AN: 3246

South Asian (SAS) AF: 0.578 AC: 1321 AN: 2287

European-Finnish (FIN) AF: 0.440 AC: 2277 AN: 5172

Middle Eastern (MID) AF: 0.368 AC: 78 AN: 212

European-Non Finnish (NFE) AF: 0.344 AC: 17834 AN: 51780

Other (OTH) AF: 0.364 AC: 529 AN: 1452

Alfa AF: 0.148 Hom.: 547

Asia WGS AF: 0.572 AC: 1438 AN: 2518

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		0.47
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: rs3048712; hg19: chrX-79277627; COSMIC: COSV107476108; COSMIC: COSV107476108;