Genetic Variant TBX21:p.Pro38Leu (chr17-47733567-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_013351.2(TBX21):c.113C>T(p.Pro38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P38Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

TBX21
NM_013351.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.415

Publications

0 publications found

Variant links:

Genes affected

TBX21 (HGNC:11599): (T-box transcription factor 21) 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 is the human ortholog of mouse Tbx21/Tbet gene. Studies in mouse show that Tbx21 protein is a Th1 cell-specific transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (IFNG). Expression of the human ortholog also correlates with IFNG expression in Th1 and natural killer cells, suggesting a role for this gene in initiating Th1 lineage development from naive Th precursor cells. [provided by RefSeq, Jul 2008]

TBX21 Gene-Disease associations (from GenCC):

asthma, nasal polyps, and aspirin intolerance
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia
immunodeficiency 88
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

TBX21 links:

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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=0.24470755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	NM_013351.2	MANE Select	c.113C>T	p.Pro38Leu	missense	Exon 1 of 6	NP_037483.1	Q9UL17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBX21	ENST00000177694.2	TSL:1 MANE Select	c.113C>T	p.Pro38Leu	missense	Exon 1 of 6	ENSP00000177694.1	Q9UL17
TBX21	ENST00000906368.1		c.113C>T	p.Pro38Leu	missense	Exon 1 of 7	ENSP00000576427.1
TBX21	ENST00000581328.1	TSL:2	n.143C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

71640

AF XY:

0.0000239

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1321104

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

651296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26508

American (AMR)

AF:

0.00

AC:

AN:

24772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22970

East Asian (EAS)

AF:

0.00

AC:

AN:

28332

South Asian (SAS)

AF:

0.0000138

AC:

AN:

72264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35400

Middle Eastern (MID)

AF:

0.000239

AC:

AN:

4178

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051912

Other (OTH)

AF:

0.00

AC:

AN:

54768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.34

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.90

PhyloP100

0.41

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Benign

0.23

Sift

Benign

0.067

Sift4G

Benign

0.18

Polyphen

0.035

Vest4

0.26

MutPred

0.28

Gain of sheet (P = 0.0043)

MVP

0.32

MPC

1.9

ClinPred

0.032

GERP RS

0.30

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.057

gMVP

0.45

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over