chrX-80023047-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001109878.2(TBX22):c.176-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,208,342 control chromosomes in the GnomAD database, including 24 homozygotes. There are 2,345 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 0 hom., 139 hem., cov: 22)

Exomes 𝑓: 0.0065 ( 24 hom. 2206 hem. )

Consequence

TBX22
NM_001109878.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.27

Publications

0 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), Orphanet, G2P
Abruzzo-Erickson syndrome
Inheritance: XL Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

TBX22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-80023047-C-A is Benign according to our data. Variant chrX-80023047-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0044 (489/111228) while in subpopulation NFE AF = 0.00779 (413/53014). AF 95% confidence interval is 0.00717. There are 0 homozygotes in GnomAd4. There are 139 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 139 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2 link	c.176-13C>A	intron_variant	Intron 2 of 8	ENST00000373296.8	NP_001103348.1	Q9Y458-1B3KUL8
TBX22	NM_016954.2 link	c.176-13C>A	intron_variant	Intron 1 of 7		NP_058650.1	Q9Y458-1
TBX22	NM_001109879.2 link	c.-181-13C>A	intron_variant	Intron 2 of 8		NP_001103349.1	Q9Y458-2B3KUL8
TBX22	NM_001303475.1 link	c.-261C>A	upstream_gene_variant			NP_001290404.1	Q9Y458-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBX22	ENST00000373296.8 link	c.176-13C>A	intron_variant	Intron 2 of 8	5	NM_001109878.2	ENSP00000362393.3	Q9Y458-1
TBX22	ENST00000373294.8 link	c.176-13C>A	intron_variant	Intron 1 of 7	1		ENSP00000362390.5	Q9Y458-1
TBX22	ENST00000626498.2 link	n.176-13C>A	intron_variant	Intron 2 of 8	2		ENSP00000487527.1	A0A0D9SGI2
TBX22	ENST00000626877.1 link	n.-22C>A	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

490

AN:

111175

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000721

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000762

Gnomad ASJ

AF:

0.000379

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00193

Gnomad FIN

AF:

0.00600

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00779

Gnomad OTH

AF:

0.00134

GnomAD2 exomes

AF:

0.00445

AC:

807

AN:

181147

AF XY:

0.00437

show subpopulations

Gnomad AFR exome

AF:

0.000384

Gnomad AMR exome

AF:

0.000293

Gnomad ASJ exome

AF:

0.000403

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00592

Gnomad NFE exome

AF:

0.00796

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00647

AC:

7100

AN:

1097114

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

2206

AN XY:

362558

show subpopulations

African (AFR)

AF:

0.000606

AC:

AN:

26386

American (AMR)

AF:

0.000398

AC:

AN:

35176

Ashkenazi Jewish (ASJ)

AF:

0.000465

AC:

AN:

19371

East Asian (EAS)

AF:

0.00

AC:

AN:

30173

South Asian (SAS)

AF:

0.00178

AC:

AN:

54006

European-Finnish (FIN)

AF:

0.00726

AC:

294

AN:

40504

Middle Eastern (MID)

AF:

0.000739

AC:

AN:

4057

European-Non Finnish (NFE)

AF:

0.00765

AC:

6434

AN:

841393

Other (OTH)

AF:

0.00508

AC:

234

AN:

46048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

234

468

703

937

1171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00440

AC:

489

AN:

111228

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

139

AN XY:

33412

show subpopulations

African (AFR)

AF:

0.000720

AC:

AN:

30563

American (AMR)

AF:

0.000762

AC:

AN:

10505

Ashkenazi Jewish (ASJ)

AF:

0.000379

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3519

South Asian (SAS)

AF:

0.00155

AC:

AN:

2577

European-Finnish (FIN)

AF:

0.00600

AC:

AN:

5999

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00779

AC:

413

AN:

53014

Other (OTH)

AF:

0.00132

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00585

Hom.:

202

Bravo

AF:

0.00360

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cleft palate with or without ankyloglossia, X-linked

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TBX22: BS1 -

Aug 18, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

TBX22-related disorder

Benign:1

Jun 12, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.9

(source)

DANN

Benign

0.69

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over