X-80022128-GGTTTTGTTTT-GGTTTTGTTTTGTTTT

Variant names:

• chrX-80022128-G-GGTTTT
• rs3048712
• NM_001109878.2:c.-2-119_-2-115dupGTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001109878.2(TBX22):​c.-2-119_-2-115dupGTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 552,501 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., 4 hem., cov: 7)
  • Exomes 𝑓: 0.00023 (0 hom. 30 hem.)
• Consequence: TBX22 NM_001109878.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000187 (20/106765) while in subpopulation EAS AF= 0.00122 (4/3276). AF 95% confidence interval is 0.000416. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 7. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2	c.-2-119_-2-115dupGTTTT		intron_variant	Intron 1 of 8	ENST00000373296.8	NP_001103348.1
TBX22	NM_001109879.2	c.-358-119_-358-115dupGTTTT		intron_variant	Intron 1 of 8		NP_001103349.1
TBX22	NM_016954.2	c.-142_-141insGTTTT		upstream_gene_variant			NP_058650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX22	ENST00000373296.8	c.-2-140_-2-139insGTTTT		intron_variant	Intron 1 of 8	5	NM_001109878.2	ENSP00000362393.3
TBX22	ENST00000476373.1	n.120-140_120-139insGTTTT		intron_variant	Intron 1 of 1	3
TBX22	ENST00000626498.2	n.-2-140_-2-139insGTTTT		intron_variant	Intron 1 of 8	2		ENSP00000487527.1
TBX22	ENST00000373294.8	c.-142_-141insGTTTT		upstream_gene_variant		1		ENSP00000362390.5

Frequencies

GnomAD3 genomes AF: 0.000187 AC: 20 AN: 106765 Hom.: 0 Cov.: 7 AF XY: 0.000135 AC XY: 4 AN XY: 29543

Gnomad AFR AF: 0.0000341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00122

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000385

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000231

Gnomad OTH AF: 0.000696

GnomAD4 exome AF: 0.000231 AC: 103 AN: 445736 Hom.: 0 AF XY: 0.000216 AC XY: 30 AN XY: 139198

Gnomad4 AFR exome AF: 0.000339

Gnomad4 AMR exome AF: 0.000237

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000419

Gnomad4 SAS exome AF: 0.000158

Gnomad4 FIN exome AF: 0.0000879

Gnomad4 NFE exome AF: 0.000238

Gnomad4 OTH exome AF: 0.000596

GnomAD4 genome AF: 0.000187 AC: 20 AN: 106765 Hom.: 0 Cov.: 7 AF XY: 0.000135 AC XY: 4 AN XY: 29543

Gnomad4 AFR AF: 0.0000341

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00122

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000385

Gnomad4 NFE AF: 0.000231

Gnomad4 OTH AF: 0.000696

ClinVar

Not reported in ClinVar

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;