rs104894943

Positions:

• chrX-80026849-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001109878.2(TBX22):​c.779C>T​(p.Thr260Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TBX22 NM_001109878.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.14

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993
• PP5: Variant X-80026849-C-T is Pathogenic according to our data. Variant chrX-80026849-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 11329.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-80026849-C-T is described in UniProt as null. Variant chrX-80026849-C-T is described in UniProt as null. Variant chrX-80026849-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX22	NM_001109878.2	c.779C>T	p.Thr260Met	missense_variant	6/9	ENST00000373296.8	NP_001103348.1
TBX22	NM_016954.2	c.779C>T	p.Thr260Met	missense_variant	5/8		NP_058650.1
TBX22	NM_001109879.2	c.419C>T	p.Thr140Met	missense_variant	6/9		NP_001103349.1
TBX22	NM_001303475.1	c.419C>T	p.Thr140Met	missense_variant	4/7		NP_001290404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX22	ENST00000373296.8	c.779C>T	p.Thr260Met	missense_variant	6/9	5	NM_001109878.2	ENSP00000362393	P1
TBX22	ENST00000373294.8	c.779C>T	p.Thr260Met	missense_variant	5/8	1		ENSP00000362390	P1
TBX22	ENST00000626877.1	n.658C>T		non_coding_transcript_exon_variant	4/7	1
TBX22	ENST00000626498.2	c.*391C>T		3_prime_UTR_variant, NMD_transcript_variant	6/9	2		ENSP00000487527

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cleft palate with ankyloglossia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.67
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D;D
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.0	H;H
MutationTaster	Benign	1.0	A;A;A;A
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.94		Gain of stability (P = 0.0341);Gain of stability (P = 0.0341);
MVP		0.94
MPC		0.67
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.94
gMVP		0.85

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

LitVar

Other links and lift over

dbSNP: rs104894943; hg19: chrX-79282348; COSMIC: COSV64785482; COSMIC: COSV64785482;