X-80014867-A-G

Variant names:

• chrX-80014867-A-G
• rs147593294
• NM_001109878.2:c.-23A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001109878.2(TBX22):​c.-23A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 112,082 control chromosomes in the GnomAD database, including 3 homozygotes. There are 72 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 0.0026 (3 hom., 72 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TBX22 NM_001109878.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.451
• 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

ENSG00000300464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-80014867-A-G is Benign according to our data. Variant chrX-80014867-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 368662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00264 (296/112082) while in subpopulation AFR AF = 0.00854 (264/30902). AF 95% confidence interval is 0.0077. There are 3 homozygotes in GnomAd4. There are 72 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.-23A>G		5_prime_UTR	Exon 1 of 9	NP_001103348.1	Q9Y458-1
	TBX22	NM_001109879.2		c.-379A>G		5_prime_UTR	Exon 1 of 9	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.-23A>G		5_prime_UTR	Exon 1 of 9	ENSP00000362393.3	Q9Y458-1
	TBX22	ENST00000476373.1	TSL:3	n.99A>G		non_coding_transcript_exon	Exon 1 of 2
	TBX22	ENST00000626498.2	TSL:2	n.-23A>G		non_coding_transcript_exon	Exon 1 of 9	ENSP00000487527.1	A0A0D9SGI2

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 295 AN: 112034 Hom.: 3 Cov.: 23

Gnomad AFR AF: 0.00853

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00274

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: 0.00199

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 138 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 113

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.00264 AC: 296 AN: 112082 Hom.: 3 Cov.: 23 AF XY: 0.00210 AC XY: 72 AN XY: 34254

African (AFR) AF: 0.00854 AC: 264 AN: 30902

American (AMR) AF: 0.00274 AC: 29 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.00 AC: 0 AN: 2689

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53183

Other (OTH) AF: 0.00197 AC: 3 AN: 1524

Alfa AF: 0.00157 Hom.: 4

Bravo AF: 0.00333

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cleft palate with or without ankyloglossia, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.31
PhyloP100		-0.45
PromoterAI		0.057	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs147593294; hg19: chrX-79270366;