17-47733780-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013351.2(TBX21):c.326C>G(p.Ala109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,543,306 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

TBX21
NM_013351.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.51

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069426894).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2 link	c.326C>G	p.Ala109Gly	missense_variant	Exon 1 of 6	ENST00000177694.2	NP_037483.1	Q9UL17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX21	ENST00000177694.2 link	c.326C>G	p.Ala109Gly	missense_variant	Exon 1 of 6	1	NM_013351.2	ENSP00000177694.1		Q9UL17
TBX21	ENST00000581328.1 link	n.356C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000941

AC:

143

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00112

AC:

158

AN:

140536

Hom.:

AF XY:

0.00126

AC XY:

AN XY:

77592

show subpopulations

Gnomad AFR exome

AF:

0.000565

Gnomad AMR exome

AF:

0.0000889

Gnomad ASJ exome

AF:

0.00650

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00122

AC:

1701

AN:

1391184

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

866

AN XY:

687216

show subpopulations

Gnomad4 AFR exome

AF:

0.000231

Gnomad4 AMR exome

AF:

0.0000884

Gnomad4 ASJ exome

AF:

0.00585

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.000104

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000940

AC:

143

AN:

152122

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000684

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000657

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Asthma, nasal polyps, and aspirin intolerance

Uncertain:1

Aug 15, 2019

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TBX21 NM_013351.1 exon1 p.Ala109Gly (c.326C>G): This variant has not been reported in the literature but is present in 0.1% (32/22742) of South Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-45811146-C-G). This variant amino acid Glycine (Gly) is present in two species (Black flying fox, Megabat) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Asthma, nasal polyps, and aspirin intolerance;C5562026:Immunodeficiency 88

Uncertain:1

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.17

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.37

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.81

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.27

REVEL

Benign

0.23

Sift

Benign

0.34

Sift4G

Benign

0.69

Polyphen

0.0020

Vest4

0.093

MVP

0.52

MPC

1.7

ClinPred

0.0043

GERP RS

2.5

Varity_R

0.092

gMVP

0.33

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over