chrX-80014614-T-A

Variant names:

• chrX-80014614-T-A
• rs41307258
• ENST00000772035.1:n.100-752A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000772035.1(ENSG00000300464):​n.100-752A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 111,499 control chromosomes in the GnomAD database, including 301 homozygotes. There are 1,900 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (301 hom., 1899 hem., cov: 23)
  • Exomes 𝑓: 0.14 (0 hom. 1 hem.)
• Consequence: ENSG00000300464 ENST00000772035.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 5 publications found

Genes affected

ENSG00000300464 (HGNC:):

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: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Abruzzo-Erickson syndrome

  Inheritance: XL Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000772035.1. 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.-276T>A		upstream_gene	N/A	NP_001103348.1
	TBX22	NM_001109879.2		c.-632T>A		upstream_gene	N/A	NP_001103349.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000300464	ENST00000772035.1		n.100-752A>T		intron	N/A
	TBX22	ENST00000373296.8	TSL:5 MANE Select	c.-276T>A		upstream_gene	N/A	ENSP00000362393.3
	TBX22	ENST00000476373.1	TSL:3	n.-155T>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 5793 AN: 111434 Hom.: 300 Cov.: 23

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0212

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.0252

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0662

GnomAD4 exome AF: 0.143 AC: 1 AN: 7 Hom.: 0 AF XY: 0.200 AC XY: 1 AN XY: 5

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 1

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 1 AN: 5

Other (OTH) AF: 0.00 AC: 0 AN: 1

GnomAD4 genome AF: 0.0520 AC: 5800 AN: 111492 Hom.: 301 Cov.: 23 AF XY: 0.0563 AC XY: 1899 AN XY: 33708

African (AFR) AF: 0.0277 AC: 850 AN: 30737

American (AMR) AF: 0.0617 AC: 650 AN: 10527

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 56 AN: 2639

East Asian (EAS) AF: 0.430 AC: 1479 AN: 3438

South Asian (SAS) AF: 0.106 AC: 280 AN: 2646

European-Finnish (FIN) AF: 0.0961 AC: 579 AN: 6024

Middle Eastern (MID) AF: 0.0321 AC: 7 AN: 218

European-Non Finnish (NFE) AF: 0.0331 AC: 1758 AN: 53066

Other (OTH) AF: 0.0674 AC: 102 AN: 1513

Alfa AF: 0.0404 Hom.: 208

Bravo AF: 0.0551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.94
PromoterAI		-0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs41307258; hg19: chrX-79270113;