NM_001109878.2:c.-103G>A

Variant names:

• chrX-80014787-G-A
• rs73496511
• NM_001109878.2:c.-103G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001109878.2(TBX22):​c.-103G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 112,233 control chromosomes in the GnomAD database, including 68 homozygotes. There are 660 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (68 hom., 660 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TBX22 NM_001109878.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.289
• Publications: 1 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=-0.86).
• BP6: Variant X-80014787-G-A is Benign according to our data. Variant chrX-80014787-G-A is described in ClinVar as Benign. ClinVar VariationId is 368660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

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.-103G>A		5_prime_UTR	Exon 1 of 9	NP_001103348.1	Q9Y458-1
	TBX22	NM_001109879.2		c.-459G>A		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.-103G>A		5_prime_UTR	Exon 1 of 9	ENSP00000362393.3	Q9Y458-1
	TBX22	ENST00000476373.1	TSL:3	n.19G>A		non_coding_transcript_exon	Exon 1 of 2
	TBX22	ENST00000626498.2	TSL:2	n.-103G>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000487527.1	A0A0D9SGI2

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 2525 AN: 112182 Hom.: 68 Cov.: 22

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00990

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000369

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.0206

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 54 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34

African (AFR) AF: 0.00 AC: 0 AN: 1

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: 1

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0226 AC: 2531 AN: 112233 Hom.: 68 Cov.: 22 AF XY: 0.0192 AC XY: 660 AN XY: 34411

African (AFR) AF: 0.0773 AC: 2385 AN: 30857

American (AMR) AF: 0.00989 AC: 105 AN: 10622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3527

South Asian (SAS) AF: 0.000370 AC: 1 AN: 2704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53249

Other (OTH) AF: 0.0203 AC: 31 AN: 1527

Alfa AF: 0.00417 Hom.: 20

Bravo AF: 0.0266

ClinVar

ClinVar submissions

Significance: 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	-0.86
CADD	Benign	3.8
DANN	Benign	0.40
PhyloP100		0.29
PromoterAI		0.027	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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: rs73496511; hg19: chrX-79270286;