X-80022128-GGTTTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001109878.2(TBX22):c.-2-119_-2-115del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 551,747 control chromosomes in the GnomAD database, including 29,487 homozygotes. There are 67,005 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (5222 hom., 9607 hem., cov: 6)
  • Exomes 𝑓: 0.38 (24265 hom. 57398 hem.)
• Consequence: TBX22 NM_001109878.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.467

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-80022128-GGTTTT-G is Benign according to our data. Variant chrX-80022128-GGTTTT-G is described in ClinVar as [Benign]. Clinvar id is 1271765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX22	NM_001109878.2	c.-2-119_-2-115del		intron_variant		ENST00000373296.8
TBX22	NM_001109879.2	c.-358-119_-358-115del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX22	ENST00000373296.8	c.-2-119_-2-115del		intron_variant		5	NM_001109878.2	P1
TBX22	ENST00000626498.2	c.-2-119_-2-115del		intron_variant, NMD_transcript_variant		2
TBX22	ENST00000476373.1	n.120-119_120-115del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 37490 AN: 106541 Hom.: 5224 Cov.: 6 AF XY: 0.327 AC XY: 9600 AN XY: 29377

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.384 AC: 170963 AN: 445162 Hom.: 24265 AF XY: 0.413 AC XY: 57398 AN XY: 138838

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.352 AC: 37489 AN: 106585 Hom.: 5222 Cov.: 6 AF XY: 0.326 AC XY: 9607 AN XY: 29433

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.364

Asia WGS AF: 0.572 AC: 1438 AN: 2518

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3048712; hg19: chrX-79277627;