dbSNP rs104894945: TBX22:p.Glu56Lys (chrX-80022435-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001109878.2(TBX22):c.166G>A(p.Glu56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,070,105 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000056 ( 0 hom. 2 hem. )

Consequence

TBX22
NM_001109878.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.055299222).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2 link	c.166G>A	p.Glu56Lys	missense_variant	Exon 2 of 9	ENST00000373296.8	NP_001103348.1	Q9Y458-1B3KUL8
TBX22	NM_016954.2 link	c.166G>A	p.Glu56Lys	missense_variant	Exon 1 of 8		NP_058650.1	Q9Y458-1
TBX22	NM_001109879.2 link	c.-191G>A		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.166G>A	p.Glu56Lys	missense_variant	Exon 2 of 9	5	NM_001109878.2	ENSP00000362393.3	Q9Y458-1
TBX22	ENST00000373294.8 link	c.166G>A	p.Glu56Lys	missense_variant	Exon 1 of 8	1		ENSP00000362390.5	Q9Y458-1
TBX22	ENST00000476373.1 link	n.287G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
TBX22	ENST00000626498.2 link	n.166G>A		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000487527.1	A0A0D9SGI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000561

AC:

AN:

1070105

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

347239

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000352

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000483

Gnomad4 OTH exome

AF:

0.0000222

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.1

DANN

Benign

0.95

DEOGEN2

Benign

0.060

T;T

FATHMM_MKL

Benign

0.082

M_CAP

Benign

0.026

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.89

L;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.16

Sift

Benign

0.16

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0070

B;B

Vest4

0.15

MutPred

0.25

Gain of MoRF binding (P = 0.0101);Gain of MoRF binding (P = 0.0101);

MVP

0.21

MPC

0.17

ClinPred

0.038

GERP RS

0.72

Varity_R

0.056

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over