Variant rs770084170 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.170C>G(p.Pro57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,068,852 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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 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=0.047418714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2 link	c.170C>G	p.Pro57Arg	missense_variant	Exon 2 of 9	ENST00000373296.8	NP_001103348.1	Q9Y458-1B3KUL8
TBX22	NM_016954.2 link	c.170C>G	p.Pro57Arg	missense_variant	Exon 1 of 8		NP_058650.1	Q9Y458-1
TBX22	NM_001109879.2 link	c.-187C>G		5_prime_UTR_variant	Exon 2 of 9		NP_001103349.1	Q9Y458-2B3KUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBX22	ENST00000373296.8 link	c.170C>G	p.Pro57Arg	missense_variant	Exon 2 of 9	5	NM_001109878.2	ENSP00000362393.3	Q9Y458-1
TBX22	ENST00000373294.8 link	c.170C>G	p.Pro57Arg	missense_variant	Exon 1 of 8	1		ENSP00000362390.5	Q9Y458-1
TBX22	ENST00000476373.1 link	n.291C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
TBX22	ENST00000626498.2 link	n.170C>G		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000487527.1	A0A0D9SGI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000751

AC:

AN:

133145

Hom.:

AF XY:

0.00

AC XY:

AN XY:

42147

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:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000187

AC:

AN:

1068852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

346862

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:

0.00000242

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000873

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.80

DANN

Benign

0.57

DEOGEN2

Benign

0.062

T;T

FATHMM_MKL

Benign

0.026

M_CAP

Benign

0.021

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.069

Sift

Benign

0.40

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.068

B;B

Vest4

0.17

MutPred

0.27

Gain of MoRF binding (P = 0.0053);Gain of MoRF binding (P = 0.0053);

MVP

0.29

MPC

0.16

ClinPred

0.015

GERP RS

-3.6

Varity_R

0.038

gMVP

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over