dbSNP rs3048712: TBX22:c.-2-124_-2-115delGTTTTGTTTT (chrX-80022128-GGTTTTGTTTT-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001109878.2(TBX22):c.-2-124_-2-115delGTTTTGTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 552,496 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000094 ( 0 hom., 0 hem., cov: 6)

Exomes 𝑓: 0.000018 ( 0 hom. 5 hem. )

Consequence

TBX22
NM_001109878.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.726

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

cleft palate with or without ankyloglossia, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Abruzzo-Erickson syndrome
Inheritance: XL Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

TBX22 links:

ENSG00000300464 (HGNC:):

ENSG00000300464 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBX22	NM_001109878.2	MANE Select	c.-2-124_-2-115delGTTTTGTTTT	intron	N/A	NP_001103348.1	Q9Y458-1
TBX22	NM_001109879.2		c.-358-124_-358-115delGTTTTGTTTT	intron	N/A	NP_001103349.1	Q9Y458-2
TBX22	NM_016954.2		c.-141_-132delGTTTTGTTTT	upstream_gene	N/A	NP_058650.1	Q9Y458-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBX22	ENST00000373296.8	TSL:5 MANE Select	c.-2-139_-2-130delGTTTTGTTTT	intron	N/A	ENSP00000362393.3	Q9Y458-1
TBX22	ENST00000968708.1		c.-2-139_-2-130delGTTTTGTTTT	intron	N/A	ENSP00000638767.1
TBX22	ENST00000476373.1	TSL:3	n.120-139_120-130delGTTTTGTTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000937

AC:

AN:

106765

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000101

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

445687

Hom.:

AF XY:

0.0000359

AC XY:

AN XY:

139163

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11804

American (AMR)

AF:

0.000118

AC:

AN:

16878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11914

East Asian (EAS)

AF:

0.00

AC:

AN:

23844

South Asian (SAS)

AF:

0.0000946

AC:

AN:

31719

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1911

European-Non Finnish (NFE)

AF:

0.0000103

AC:

AN:

289993

Other (OTH)

AF:

0.00

AC:

AN:

23492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000936

AC:

AN:

106809

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29599

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29401

American (AMR)

AF:

0.000101

AC:

AN:

9903

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2578

East Asian (EAS)

AF:

0.00

AC:

AN:

3264

South Asian (SAS)

AF:

0.00

AC:

AN:

2292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51862

Other (OTH)

AF:

0.00

AC:

AN:

1454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

547

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over