Variant X-80022435-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001109878.2(TBX22):c.166G>C(p.Glu56Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,181,665 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000093 ( 0 hom. 1 hem. )

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.382

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044565946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBX22	NM_001109878.2 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant	2/9	ENST00000373296.8	NP_001103348.1
TBX22	NM_016954.2 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant	1/8		NP_058650.1
TBX22	NM_001109879.2 linkuse as main transcript	c.-191G>C		5_prime_UTR_variant	2/9		NP_001103349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX22	ENST00000373296.8 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant	2/9	5	NM_001109878.2	ENSP00000362393	P1	Q9Y458-1
TBX22	ENST00000373294.8 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant	1/8	1		ENSP00000362390	P1	Q9Y458-1
TBX22	ENST00000476373.1 linkuse as main transcript	n.287G>C		non_coding_transcript_exon_variant	2/2	3
TBX22	ENST00000626498.2 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000487527

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111561

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33731

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000148

AC:

AN:

134729

Hom.:

AF XY:

0.00

AC XY:

AN XY:

42401

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000934

AC:

AN:

1070104

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

347238

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:

0.0000121

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111561

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33731

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

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

Dec 20, 2021

The c.166G>C (p.E56Q) alteration is located in exon 2 (coding exon 1) of the TBX22 gene. This alteration results from a G to C substitution at nucleotide position 166, causing the glutamic acid (E) at amino acid position 56 to be replaced by a glutamine (Q). 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

0.070

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.27

DANN

Benign

0.63

DEOGEN2

Benign

0.034

T;T

FATHMM_MKL

Benign

0.058

M_CAP

Benign

0.027

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.33

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.11

Sift

Benign

0.35

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.013

B;B

Vest4

0.057

MutPred

0.15

Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);

MVP

0.24

MPC

0.15

ClinPred

0.98

GERP RS

0.72

Varity_R

0.069

gMVP

0.23

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