dbSNP rs41307258: ENSG00000300464:n.100-752A>T (chrX-80014614-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.939

Publications

5 publications found

Variant links:

Genes affected

ENSG00000300464 (HGNC:):

ENSG00000300464 links:

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

TBX22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX22	NM_001109878.2 link	c.-276T>A		upstream_gene_variant		ENST00000373296.8	NP_001103348.1	Q9Y458-1B3KUL8
TBX22	NM_001109879.2 link	c.-632T>A		upstream_gene_variant			NP_001103349.1	Q9Y458-2B3KUL8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000300464	ENST00000772035.1 link	n.100-752A>T	intron_variant	Intron 1 of 1
TBX22	ENST00000373296.8 link	c.-276T>A	upstream_gene_variant		5	NM_001109878.2	ENSP00000362393.3	Q9Y458-1
TBX22	ENST00000476373.1 link	n.-155T>A	upstream_gene_variant		3
TBX22	ENST00000626498.2 link	n.-276T>A	upstream_gene_variant		2		ENSP00000487527.1	A0A0D9SGI2

Frequencies

GnomAD3 genomes

AF:

0.0520

AC:

5793

AN:

111434

Hom.:

300

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.200

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0520

AC:

5800

AN:

111492

Hom.:

301

Cov.:

AF XY:

0.0563

AC XY:

1899

AN XY:

33708

show subpopulations

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:

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:

AN:

218

European-Non Finnish (NFE)

AF:

0.0331

AC:

1758

AN:

53066

Other (OTH)

AF:

0.0674

AC:

102

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

173

346

519

692

865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0404

Hom.:

208

Bravo

AF:

0.0551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.94

PromoterAI

-0.025

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over