NM_001109878.2:c.166G>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 16/21 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

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:

ENSG00000300464 (HGNC:):

ENSG00000300464 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TBX22	NM_001109878.2	MANE Select	c.166G>C	p.Glu56Gln	missense	Exon 2 of 9	NP_001103348.1
TBX22	NM_016954.2		c.166G>C	p.Glu56Gln	missense	Exon 1 of 8	NP_058650.1
TBX22	NM_001109879.2		c.-191G>C		5_prime_UTR	Exon 2 of 9	NP_001103349.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TBX22	ENST00000373296.8	TSL:5 MANE Select	c.166G>C	p.Glu56Gln	missense	Exon 2 of 9	ENSP00000362393.3
TBX22	ENST00000373294.8	TSL:1	c.166G>C	p.Glu56Gln	missense	Exon 1 of 8	ENSP00000362390.5
TBX22	ENST00000924637.1		c.166G>C	p.Glu56Gln	missense	Exon 1 of 8	ENSP00000594696.1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111561

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000148

AC:

AN:

134729

AF XY:

0.00

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:

0.0000360

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

African (AFR)

AF:

0.00

AC:

AN:

25499

American (AMR)

AF:

0.00

AC:

AN:

30766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18884

East Asian (EAS)

AF:

0.00

AC:

AN:

28371

South Asian (SAS)

AF:

0.00

AC:

AN:

50999

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38695

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3607

European-Non Finnish (NFE)

AF:

0.0000121

AC:

AN:

828243

Other (OTH)

AF:

0.00

AC:

AN:

45040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.00000896

AC:

AN:

111561

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33731

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30541

American (AMR)

AF:

0.00

AC:

AN:

10593

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3524

South Asian (SAS)

AF:

0.00

AC:

AN:

2635

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6121

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53089

Other (OTH)

AF:

0.00

AC:

AN:

1494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000215

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.27

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.034

FATHMM_MKL

Benign

0.058

M_CAP

Benign

0.027

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.33

PhyloP100

-0.38

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.20

REVEL

Benign

0.11

Sift

Benign

0.35

Sift4G

Benign

0.64

Polyphen

0.013

Vest4

0.057

MutPred

0.15

Loss of loop (P = 0.0603)

MVP

0.24

MPC

0.15

ClinPred

0.98

GERP RS

0.72

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.069

gMVP

0.23

Mutation Taster

=92/8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over