Variant X-80022322-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001109878.2(TBX22):c.53G>T(p.Arg18Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 111,260 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBX22	NM_001109878.2 linkuse as main transcript	c.53G>T	p.Arg18Ile	missense_variant	2/9	ENST00000373296.8
TBX22	NM_016954.2 linkuse as main transcript	c.53G>T	p.Arg18Ile	missense_variant	1/8
TBX22	NM_001109879.2 linkuse as main transcript	c.-304G>T		5_prime_UTR_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX22	ENST00000373296.8 linkuse as main transcript	c.53G>T	p.Arg18Ile	missense_variant	2/9	5	NM_001109878.2	P1	Q9Y458-1
TBX22	ENST00000373294.8 linkuse as main transcript	c.53G>T	p.Arg18Ile	missense_variant	1/8	1		P1	Q9Y458-1
TBX22	ENST00000476373.1 linkuse as main transcript	n.174G>T		non_coding_transcript_exon_variant	2/2	3
TBX22	ENST00000626498.2 linkuse as main transcript	c.53G>T	p.Arg18Ile	missense_variant, NMD_transcript_variant	2/9	2

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33476

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000952

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.53G>T (p.R18I) alteration is located in exon 2 (coding exon 1) of the TBX22 gene. This alteration results from a G to T substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.19

T;T

FATHMM_MKL

Uncertain

0.80

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.078

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.86

P;P

Vest4

0.42

MutPred

0.33

Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);

MVP

0.70

MPC

0.69

ClinPred

0.81

GERP RS

2.7

Varity_R

0.16

gMVP

0.44

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