X-80022341-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001109878.2(TBX22):c.72C>T(p.Leu24Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,209,470 control chromosomes in the GnomAD database, including 22 homozygotes. There are 545 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 10 hom., 223 hem., cov: 22)

Exomes 𝑓: 0.0011 ( 12 hom. 322 hem. )

Consequence

TBX22
NM_001109878.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.04

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-80022341-C-T is Benign according to our data. Variant chrX-80022341-C-T is described in ClinVar as [Benign]. Clinvar id is 368664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-80022341-C-T is described in Lovd as [Likely_benign]. Variant chrX-80022341-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00803 (896/111597) while in subpopulation AFR AF= 0.0257 (787/30642). AF 95% confidence interval is 0.0242. There are 10 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2 link	c.72C>T	p.Leu24Leu	synonymous_variant	Exon 2 of 9	ENST00000373296.8	NP_001103348.1	Q9Y458-1B3KUL8
TBX22	NM_016954.2 link	c.72C>T	p.Leu24Leu	synonymous_variant	Exon 1 of 8		NP_058650.1	Q9Y458-1
TBX22	NM_001109879.2 link	c.-285C>T		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.72C>T	p.Leu24Leu	synonymous_variant	Exon 2 of 9	5	NM_001109878.2	ENSP00000362393.3	Q9Y458-1
TBX22	ENST00000373294.8 link	c.72C>T	p.Leu24Leu	synonymous_variant	Exon 1 of 8	1		ENSP00000362390.5	Q9Y458-1
TBX22	ENST00000476373.1 link	n.193C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
TBX22	ENST00000626498.2 link	n.72C>T		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000487527.1	A0A0D9SGI2

Frequencies

GnomAD3 genomes

AF:

0.00792

AC:

883

AN:

111547

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

214

AN XY:

33769

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00540

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000753

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00297

AC:

543

AN:

182765

Hom.:

AF XY:

0.00202

AC XY:

136

AN XY:

67285

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00847

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00112

AC:

1230

AN:

1097873

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

322

AN XY:

363239

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00543

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000368

Gnomad4 OTH exome

AF:

0.00395

GnomAD4 genome

AF:

0.00803

AC:

896

AN:

111597

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

223

AN XY:

33829

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.00539

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.0139

Alfa

AF:

0.00494

Hom.:

Bravo

AF:

0.00936

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cleft palate with or without ankyloglossia, X-linked

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.78

DANN

Benign

0.83

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over