Genetic Variant TBX21:p.Gly130Gly (chr17-47733844-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013351.2(TBX21):c.390A>G(p.Gly130Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,609,696 control chromosomes in the GnomAD database, including 62,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6253 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55908 hom. )

Consequence

TBX21
NM_013351.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.469

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-47733844-A-G is Benign according to our data. Variant chr17-47733844-A-G is described in ClinVar as [Benign]. Clinvar id is 1334938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-47733844-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.469 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX21	NM_013351.2 link	c.390A>G	p.Gly130Gly	synonymous_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.390A>G	p.Gly130Gly	synonymous_variant	Exon 1 of 6	1	NM_013351.2	ENSP00000177694.1		Q9UL17
TBX21	ENST00000581328.1 link	n.420A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42789

AN:

151746

Hom.:

6257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.296

AC:

70657

AN:

238706

Hom.:

11079

AF XY:

0.298

AC XY:

38918

AN XY:

130754

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.0982

Gnomad SAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.272

AC:

395860

AN:

1457832

Hom.:

55908

Cov.:

AF XY:

0.274

AC XY:

198834

AN XY:

725092

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.389

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.379

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.282

AC:

42805

AN:

151864

Hom.:

6253

Cov.:

AF XY:

0.284

AC XY:

21118

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.255

Hom.:

3079

Bravo

AF:

0.285

Asia WGS

AF:

0.272

AC:

949

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Immunodeficiency 88

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.7

DANN

Benign

0.73

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