chr17-47733553-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_013351.2(TBX21):​c.99C>G​(p.His33Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,487,136 control chromosomes in the GnomAD database, including 1,068 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.030 ( 157 hom., cov: 32)
Exomes 𝑓: 0.031 ( 911 hom. )

Consequence

TBX21
NM_013351.2 missense

Scores

1
17

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.991
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0011099577).
BP6
Variant 17-47733553-C-G is Benign according to our data. Variant chr17-47733553-C-G is described in ClinVar as [Benign]. Clinvar id is 2688320.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TBX21NM_013351.2 linkuse as main transcriptc.99C>G p.His33Gln missense_variant 1/6 ENST00000177694.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBX21ENST00000177694.2 linkuse as main transcriptc.99C>G p.His33Gln missense_variant 1/61 NM_013351.2 P1
TBX21ENST00000581328.1 linkuse as main transcriptn.129C>G non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
AF:
0.0301
AC:
4577
AN:
152020
Hom.:
156
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0112
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0789
Gnomad ASJ
AF:
0.0703
Gnomad EAS
AF:
0.108
Gnomad SAS
AF:
0.0534
Gnomad FIN
AF:
0.00387
Gnomad MID
AF:
0.0414
Gnomad NFE
AF:
0.0252
Gnomad OTH
AF:
0.0398
GnomAD3 exomes
AF:
0.0488
AC:
4004
AN:
82008
Hom.:
164
AF XY:
0.0474
AC XY:
2231
AN XY:
47062
show subpopulations
Gnomad AFR exome
AF:
0.0115
Gnomad AMR exome
AF:
0.0807
Gnomad ASJ exome
AF:
0.0670
Gnomad EAS exome
AF:
0.101
Gnomad SAS exome
AF:
0.0597
Gnomad FIN exome
AF:
0.00467
Gnomad NFE exome
AF:
0.0254
Gnomad OTH exome
AF:
0.0448
GnomAD4 exome
AF:
0.0309
AC:
41282
AN:
1335008
Hom.:
911
Cov.:
31
AF XY:
0.0317
AC XY:
20884
AN XY:
658392
show subpopulations
Gnomad4 AFR exome
AF:
0.00881
Gnomad4 AMR exome
AF:
0.0820
Gnomad4 ASJ exome
AF:
0.0665
Gnomad4 EAS exome
AF:
0.109
Gnomad4 SAS exome
AF:
0.0613
Gnomad4 FIN exome
AF:
0.00571
Gnomad4 NFE exome
AF:
0.0257
Gnomad4 OTH exome
AF:
0.0348
GnomAD4 genome
AF:
0.0302
AC:
4588
AN:
152128
Hom.:
157
Cov.:
32
AF XY:
0.0315
AC XY:
2343
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0114
Gnomad4 AMR
AF:
0.0790
Gnomad4 ASJ
AF:
0.0703
Gnomad4 EAS
AF:
0.108
Gnomad4 SAS
AF:
0.0534
Gnomad4 FIN
AF:
0.00387
Gnomad4 NFE
AF:
0.0252
Gnomad4 OTH
AF:
0.0398
Alfa
AF:
0.0233
Hom.:
12
Bravo
AF:
0.0342
TwinsUK
AF:
0.0245
AC:
91
ALSPAC
AF:
0.0249
AC:
96
ESP6500AA
AF:
0.00519
AC:
12
ESP6500EA
AF:
0.0163
AC:
86
ExAC
AF:
0.0213
AC:
1034
Asia WGS
AF:
0.0720
AC:
247
AN:
3450

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
19
DANN
Benign
0.58
DEOGEN2
Benign
0.24
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.40
T
MetaRNN
Benign
0.0011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
0.92
P
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.21
Sift
Benign
0.14
T
Sift4G
Benign
0.47
T
Polyphen
0.0040
B
Vest4
0.024
MutPred
0.070
Gain of sheet (P = 0.0827);
MPC
1.7
ClinPred
0.0023
T
GERP RS
0.45
Varity_R
0.055
gMVP
0.15

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.

Other links and lift over

dbSNP: rs2240017; hg19: chr17-45810919; COSMIC: COSV51596141; API