rs1156605251

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_001109878.2(TBX22):c.448A>C(p.Lys150Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,207,301 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.32

Publications

1 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: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.776

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2 link	c.448A>C	p.Lys150Gln	missense_variant	Exon 4 of 9	ENST00000373296.8	NP_001103348.1	Q9Y458-1B3KUL8
TBX22	NM_016954.2 link	c.448A>C	p.Lys150Gln	missense_variant	Exon 3 of 8		NP_058650.1	Q9Y458-1
TBX22	NM_001109879.2 link	c.88A>C	p.Lys30Gln	missense_variant	Exon 4 of 9		NP_001103349.1	Q9Y458-2B3KUL8
TBX22	NM_001303475.1 link	c.88A>C	p.Lys30Gln	missense_variant	Exon 2 of 7		NP_001290404.1	Q9Y458-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX22	ENST00000373296.8 link	c.448A>C	p.Lys150Gln	missense_variant	Exon 4 of 9	5	NM_001109878.2	ENSP00000362393.3		Q9Y458-1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000387

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183376

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1096353

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

361737

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26372

American (AMR)

AF:

0.00

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30191

South Asian (SAS)

AF:

0.00

AC:

AN:

54102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

840439

Other (OTH)

AF:

0.00

AC:

AN:

46033

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000180

AC:

AN:

110948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33148

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

30363

American (AMR)

AF:

0.00

AC:

AN:

10515

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3487

South Asian (SAS)

AF:

0.000387

AC:

AN:

2583

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52991

Other (OTH)

AF:

0.00

AC:

AN:

1496

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000302

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cleft palate;C3266076:Orofacial cleft

Uncertain:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.73

D;D

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.7

M;M

PhyloP100

8.3

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

0.49

P;P

Vest4

0.78

MutPred

0.64

Loss of methylation at K150 (P = 0.0238);Loss of methylation at K150 (P = 0.0238);

MVP

0.91

MPC

0.67

ClinPred

0.87

GERP RS

4.7

Varity_R

0.89

gMVP

0.53

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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