X-80022261-C-A

Position:

chrX-80022261-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001109878.2(TBX22):c.-2-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,208,650 control chromosomes in the GnomAD database, including 12 homozygotes. There are 364 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., 158 hem., cov: 22)

Exomes 𝑓: 0.00065 ( 5 hom. 206 hem. )

Consequence

TBX22
NM_001109878.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003026

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0620

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-80022261-C-A is Benign according to our data. Variant chrX-80022261-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 368663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00531 (588/110796) while in subpopulation AFR AF= 0.018 (548/30429). AF 95% confidence interval is 0.0168. There are 7 homozygotes in gnomad4. There are 158 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
TBX22	NM_001109878.2 linkuse as main transcript	c.-2-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000373296.8	NP_001103348.1
TBX22	NM_016954.2 linkuse as main transcript	c.-9C>A	5_prime_UTR_variant	1/8		NP_058650.1
TBX22	NM_001109879.2 linkuse as main transcript	c.-358-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001103349.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX22	ENST00000373294.8 linkuse as main transcript	c.-9C>A	5_prime_UTR_variant	1/8	1		ENSP00000362390	P1	Q9Y458-1
TBX22	ENST00000373296.8 linkuse as main transcript	c.-2-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001109878.2	ENSP00000362393	P1	Q9Y458-1
TBX22	ENST00000626498.2 linkuse as main transcript	c.-2-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2		ENSP00000487527
TBX22	ENST00000476373.1 linkuse as main transcript	n.120-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

587

AN:

110748

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

157

AN XY:

32976

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000946

Gnomad OTH

AF:

0.00406

GnomAD3 exomes

AF:

0.00191

AC:

348

AN:

182524

Hom.:

AF XY:

0.00136

AC XY:

AN XY:

67144

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000941

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000984

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000647

AC:

710

AN:

1097854

Hom.:

Cov.:

AF XY:

0.000567

AC XY:

206

AN XY:

363222

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000431

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000950

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00531

AC:

588

AN:

110796

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

158

AN XY:

33034

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.00277

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000946

Gnomad4 OTH

AF:

0.00401

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.00633

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TBX22-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Cleft palate with or without ankyloglossia, X-linked

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: -38

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