rs55760411

Variant names:

• chrX-80023047-C-A
• rs55760411
• NM_001109878.2:c.176-13C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001109878.2(TBX22):​c.176-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,208,342 control chromosomes in the GnomAD database, including 24 homozygotes. There are 2,345 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 0.0044 (0 hom., 139 hem., cov: 22)
  • Exomes 𝑓: 0.0065 (24 hom. 2206 hem.)
• Consequence: TBX22 NM_001109878.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-80023047-C-A is Benign according to our data. Variant chrX-80023047-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0044 (489/111228) while in subpopulation NFE AF = 0.00779 (413/53014). AF 95% confidence interval is 0.00717. There are 0 homozygotes in GnomAd4. There are 139 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 139 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX22	NM_001109878.2	MANE Select	c.176-13C>A		intron	N/A	NP_001103348.1	Q9Y458-1
	TBX22	NM_016954.2		c.176-13C>A		intron	N/A	NP_058650.1	Q9Y458-1
	TBX22	NM_001109879.2		c.-181-13C>A		intron	N/A	NP_001103349.1	Q9Y458-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX22	ENST00000373296.8	TSL:5 MANE Select	c.176-13C>A		intron	N/A	ENSP00000362393.3	Q9Y458-1
	TBX22	ENST00000373294.8	TSL:1	c.176-13C>A		intron	N/A	ENSP00000362390.5	Q9Y458-1
	TBX22	ENST00000924637.1		c.176-10C>A		intron	N/A	ENSP00000594696.1

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 490 AN: 111175 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000721

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000762

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.00600

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00779

Gnomad OTH AF: 0.00134

GnomAD2 exomes AF: 0.00445 AC: 807 AN: 181147 AF XY: 0.00437

Gnomad AFR exome AF: 0.000384

Gnomad AMR exome AF: 0.000293

Gnomad ASJ exome AF: 0.000403

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00592

Gnomad NFE exome AF: 0.00796

Gnomad OTH exome AF: 0.00556

GnomAD4 exome AF: 0.00647 AC: 7100 AN: 1097114 Hom.: 24 Cov.: 31 AF XY: 0.00608 AC XY: 2206 AN XY: 362558

African (AFR) AF: 0.000606 AC: 16 AN: 26386

American (AMR) AF: 0.000398 AC: 14 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.000465 AC: 9 AN: 19371

East Asian (EAS) AF: 0.00 AC: 0 AN: 30173

South Asian (SAS) AF: 0.00178 AC: 96 AN: 54006

European-Finnish (FIN) AF: 0.00726 AC: 294 AN: 40504

Middle Eastern (MID) AF: 0.000739 AC: 3 AN: 4057

European-Non Finnish (NFE) AF: 0.00765 AC: 6434 AN: 841393

Other (OTH) AF: 0.00508 AC: 234 AN: 46048

GnomAD4 genome AF: 0.00440 AC: 489 AN: 111228 Hom.: 0 Cov.: 22 AF XY: 0.00416 AC XY: 139 AN XY: 33412

African (AFR) AF: 0.000720 AC: 22 AN: 30563

American (AMR) AF: 0.000762 AC: 8 AN: 10505

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3519

South Asian (SAS) AF: 0.00155 AC: 4 AN: 2577

European-Finnish (FIN) AF: 0.00600 AC: 36 AN: 5999

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00779 AC: 413 AN: 53014

Other (OTH) AF: 0.00132 AC: 2 AN: 1512

Alfa AF: 0.00585 Hom.: 202

Bravo AF: 0.00360

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cleft palate with or without ankyloglossia, X-linked (2)
-	-	2	not provided (2)
-	-	1	TBX22-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.69
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs55760411; hg19: chrX-79278546;