rs1156605251

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PP3

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a DNA_binding_region T-box (size 187) in uniprot entity TBX22_HUMAN there are 9 pathogenic changes around while only 2 benign (82%) in NM_001109878.2

PP3

MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBX22	NM_001109878.2 linkuse as main transcript	c.448A>C	p.Lys150Gln	missense_variant	4/9	ENST00000373296.8
TBX22	NM_016954.2 linkuse as main transcript	c.448A>C	p.Lys150Gln	missense_variant	3/8
TBX22	NM_001109879.2 linkuse as main transcript	c.88A>C	p.Lys30Gln	missense_variant	4/9
TBX22	NM_001303475.1 linkuse as main transcript	c.88A>C	p.Lys30Gln	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX22	ENST00000373296.8 linkuse as main transcript	c.448A>C	p.Lys150Gln	missense_variant	4/9	5	NM_001109878.2	P1	Q9Y458-1
TBX22	ENST00000373294.8 linkuse as main transcript	c.448A>C	p.Lys150Gln	missense_variant	3/8	1		P1	Q9Y458-1
TBX22	ENST00000626877.1 linkuse as main transcript	n.327A>C		non_coding_transcript_exon_variant	2/7	1
TBX22	ENST00000626498.2 linkuse as main transcript	c.*60A>C		3_prime_UTR_variant, NMD_transcript_variant	4/9	2

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33148

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

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183376

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67816

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 SAS exome

AF:

0.0000524

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

110948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33148

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000387

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2017

- -

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

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

MutationTaster

Benign

1.0

D;D;D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over