Variant X-80022417-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001109878.2(TBX22):c.148A>T(p.Ser50Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,713 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.564

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04328212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBX22	NM_001109878.2 linkuse as main transcript	c.148A>T	p.Ser50Cys	missense_variant	2/9	ENST00000373296.8	NP_001103348.1
TBX22	NM_016954.2 linkuse as main transcript	c.148A>T	p.Ser50Cys	missense_variant	1/8		NP_058650.1
TBX22	NM_001109879.2 linkuse as main transcript	c.-209A>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.148A>T	p.Ser50Cys	missense_variant	2/9	5	NM_001109878.2	ENSP00000362393	P1	Q9Y458-1
TBX22	ENST00000373294.8 linkuse as main transcript	c.148A>T	p.Ser50Cys	missense_variant	1/8	1		ENSP00000362390	P1	Q9Y458-1
TBX22	ENST00000476373.1 linkuse as main transcript	n.269A>T		non_coding_transcript_exon_variant	2/2	3
TBX22	ENST00000626498.2 linkuse as main transcript	c.148A>T	p.Ser50Cys	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000487527

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.23e-7

AC:

AN:

1083713

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352705

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:

0.00000120

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

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2019

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.045

DANN

Benign

0.50

DEOGEN2

Benign

0.040

T;T

FATHMM_MKL

Benign

0.048

M_CAP

Benign

0.019

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.16

Sift

Benign

0.17

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.31

Loss of phosphorylation at S50 (P = 2e-04);Loss of phosphorylation at S50 (P = 2e-04);

MVP

0.10

MPC

0.15

ClinPred

0.061

GERP RS

-9.2

Varity_R

0.063

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over