X-80022435-G-T

Position:

• chrX-80022435-G-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001109878.2(TBX22):​c.166G>T​(p.Glu56Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: TBX22 NM_001109878.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.382

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-80022435-G-T is Pathogenic according to our data. Variant chrX-80022435-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 11333.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-80022435-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX22	NM_001109878.2	c.166G>T	p.Glu56Ter	stop_gained	2/9	ENST00000373296.8	NP_001103348.1
TBX22	NM_016954.2	c.166G>T	p.Glu56Ter	stop_gained	1/8		NP_058650.1
TBX22	NM_001109879.2	c.-191G>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	c.166G>T	p.Glu56Ter	stop_gained	2/9	5	NM_001109878.2	ENSP00000362393	P1
TBX22	ENST00000373294.8	c.166G>T	p.Glu56Ter	stop_gained	1/8	1		ENSP00000362390	P1
TBX22	ENST00000476373.1	n.287G>T		non_coding_transcript_exon_variant	2/2	3
TBX22	ENST00000626498.2	c.166G>T	p.Glu56Ter	stop_gained, NMD_transcript_variant	2/9	2		ENSP00000487527

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

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
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.15	N
MutationTaster	Benign	1.0	A;A;A
Vest4		0.76
GERP RS		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs104894945; hg19: chrX-79277934;