Variant X-80023051-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001109878.2(TBX22):c.176-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,208,287 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000010 ( 0 hom. 6 hem. )

Consequence

TBX22
NM_001109878.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003362

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.424

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-80023051-G-A is Benign according to our data. Variant chrX-80023051-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 736301.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TBX22	NM_001109878.2 linkuse as main transcript	c.176-9G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000373296.8
TBX22	NM_001109879.2 linkuse as main transcript	c.-181-9G>A	splice_polypyrimidine_tract_variant, intron_variant
TBX22	NM_016954.2 linkuse as main transcript	c.176-9G>A	splice_polypyrimidine_tract_variant, intron_variant
TBX22	NM_001303475.1 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TBX22	ENST00000373296.8 linkuse as main transcript	c.176-9G>A	splice_polypyrimidine_tract_variant, intron_variant	5	NM_001109878.2	P1	Q9Y458-1
TBX22	ENST00000373294.8 linkuse as main transcript	c.176-9G>A	splice_polypyrimidine_tract_variant, intron_variant	1		P1	Q9Y458-1
TBX22	ENST00000626498.2 linkuse as main transcript	c.176-9G>A	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	2
TBX22	ENST00000626877.1 linkuse as main transcript		upstream_gene_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111267

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33443

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181648

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1097020

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

362444

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111267

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33443

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

Dann

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00034

SpliceAI score (max)

0.030

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