Variant X-80022439-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001109878.2(TBX22):c.170C>T(p.Pro57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000468 in 1,068,850 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: not found (cov: 22)

Exomes 𝑓: 0.0000047 ( 0 hom. 3 hem. )

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.438

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04216045).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBX22	NM_001109878.2 linkuse as main transcript	c.170C>T	p.Pro57Leu	missense_variant	2/9	ENST00000373296.8	NP_001103348.1
TBX22	NM_016954.2 linkuse as main transcript	c.170C>T	p.Pro57Leu	missense_variant	1/8		NP_058650.1
TBX22	NM_001109879.2 linkuse as main transcript	c.-187C>T		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.170C>T	p.Pro57Leu	missense_variant	2/9	5	NM_001109878.2	ENSP00000362393	P1	Q9Y458-1
TBX22	ENST00000373294.8 linkuse as main transcript	c.170C>T	p.Pro57Leu	missense_variant	1/8	1		ENSP00000362390	P1	Q9Y458-1
TBX22	ENST00000476373.1 linkuse as main transcript	n.291C>T		non_coding_transcript_exon_variant	2/2	3
TBX22	ENST00000626498.2 linkuse as main transcript	c.170C>T	p.Pro57Leu	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000487527

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000150

AC:

AN:

133145

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

42147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000919

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000468

AC:

AN:

1068850

Hom.:

Cov.:

AF XY:

0.00000865

AC XY:

AN XY:

346862

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000163

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 27, 2024

The c.170C>T (p.P57L) alteration is located in exon 2 (coding exon 1) of the TBX22 gene. This alteration results from a C to T substitution at nucleotide position 170, causing the proline (P) at amino acid position 57 to be replaced by a leucine (L). 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

0.067

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.5

DANN

Benign

0.80

DEOGEN2

Benign

0.069

T;T

FATHMM_MKL

Benign

0.033

M_CAP

Benign

0.019

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.090

Sift

Benign

0.25

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0

B;B

Vest4

0.079

MutPred

0.23

Loss of glycosylation at P57 (P = 0.0339);Loss of glycosylation at P57 (P = 0.0339);

MVP

0.12

MPC

0.16

ClinPred

0.021

GERP RS

-3.6

Varity_R

0.046

gMVP

0.35

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