rs1194520612

Variant names:

• chr17-47733765-C-T
• rs1194520612
• NM_013351.2:c.311C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-47733765-C-T
• chr17-47733765-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013351.2(TBX21):​c.311C>T​(p.Pro104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,337,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: TBX21 NM_013351.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.596
• Publications: 0 publications found

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)

ACMG classification

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=0.14441848).

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.311C>T	p.Pro104Leu	missense	Exon 1 of 6	NP_037483.1	Q9UL17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX21	ENST00000177694.2	TSL:1 MANE Select	c.311C>T	p.Pro104Leu	missense	Exon 1 of 6	ENSP00000177694.1	Q9UL17
	TBX21	ENST00000906368.1		c.311C>T	p.Pro104Leu	missense	Exon 1 of 7	ENSP00000576427.1
	TBX21	ENST00000581328.1	TSL:2	n.341C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000224 AC: 3 AN: 1337394 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 659166

African (AFR) AF: 0.00 AC: 0 AN: 26782

American (AMR) AF: 0.00 AC: 0 AN: 23298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22948

East Asian (EAS) AF: 0.00 AC: 0 AN: 29312

South Asian (SAS) AF: 0.0000138 AC: 1 AN: 72448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5034

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1055540

Other (OTH) AF: 0.00 AC: 0 AN: 55048

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.60
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D
Sift4G	Benign	0.66	T
Polyphen		0.10	B
Vest4		0.12
MutPred		0.33		Gain of stability (P = 0.1424)
MVP		0.38
MPC		1.7
ClinPred		0.090	T
GERP RS		3.5
Varity_R		0.064
gMVP		0.39
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs1194520612; hg19: chr17-45811131;