Variant rs28649236 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000332710.8(TBX1):c.22A>G(p.Arg8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TBX1
ENST00000332710.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.712

Variant links:

Genes affected

TBX1 (HGNC:11592): (T-box transcription factor 1) 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. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

TBX1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3235361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
TBX1	NM_080647.1 linkuse as main transcript	c.22A>G	p.Arg8Gly	missense_variant	2/9	NP_542378.1
TBX1	NM_080646.2 linkuse as main transcript	c.22A>G	p.Arg8Gly	missense_variant	2/9	NP_542377.1
TBX1	NM_005992.1 linkuse as main transcript	c.22A>G	p.Arg8Gly	missense_variant	2/10	NP_005983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris	UniProt
TBX1	ENST00000332710.8 linkuse as main transcript	c.22A>G	p.Arg8Gly	missense_variant	2/9	1	ENSP00000331791	P2	O43435-3
TBX1	ENST00000329705.11 linkuse as main transcript	c.22A>G	p.Arg8Gly	missense_variant	2/9	1	ENSP00000331176	A2	O43435-1
TBX1	ENST00000359500.7 linkuse as main transcript	c.22A>G	p.Arg8Gly	missense_variant	2/10	1	ENSP00000352483	A2	O43435-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246656

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460182

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;.

Eigen

Benign

0.022

Eigen_PC

Benign

-0.0067

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

T;T;T

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

0.81

N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.98

N;N;N

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.063

T;T;T

Polyphen

0.99

.;D;.

Vest4

0.44

MutPred

0.27

Gain of catalytic residue at R8 (P = 0.0205);Gain of catalytic residue at R8 (P = 0.0205);Gain of catalytic residue at R8 (P = 0.0205);

MVP

0.99

MPC

2.2

ClinPred

0.56

GERP RS

1.1

Varity_R

0.23

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over