rs1001921296

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001379200.1(TBX1):​c.1082C>A​(p.Pro361Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,198,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P361L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

TBX1
NM_001379200.1 missense

Scores

2
1
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • conotruncal heart malformations
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • DiGeorge syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • velocardiofacial syndrome
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
  • 22q11.2 deletion syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20822075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBX1NM_001379200.1 linkc.1082C>A p.Pro361Gln missense_variant Exon 7 of 7 ENST00000649276.2 NP_001366129.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBX1ENST00000649276.2 linkc.1082C>A p.Pro361Gln missense_variant Exon 7 of 7 NM_001379200.1 ENSP00000497003.1 A0A3B3IS18

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000167
AC:
2
AN:
1198006
Hom.:
0
Cov.:
23
AF XY:
0.00000170
AC XY:
1
AN XY:
586930
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24028
American (AMR)
AF:
0.00
AC:
0
AN:
16602
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18518
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25784
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54044
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
29030
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3368
European-Non Finnish (NFE)
AF:
0.00000204
AC:
2
AN:
978166
Other (OTH)
AF:
0.00
AC:
0
AN:
48466
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
16
DANN
Benign
0.92
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.33
T;T
M_CAP
Pathogenic
0.98
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.74
T
PhyloP100
1.4
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.19
Sift
Uncertain
0.026
D;.
Sift4G
Benign
0.37
T;.
Vest4
0.16
MutPred
0.26
Gain of solvent accessibility (P = 0.0648);.;
MVP
0.81
MPC
0.56
ClinPred
0.13
T
GERP RS
1.1
gMVP
0.27
Mutation Taster
=52/48
polymorphism

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

Other links and lift over

dbSNP: rs1001921296; hg19: chr22-19753957; API