rs140730628

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033035.5(TSLP):​c.410G>A​(p.Cys137Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TSLP
NM_033035.5 missense

Scores

6
5
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.84
Variant links:
Genes affected
TSLP (HGNC:30743): (thymic stromal lymphopoietin) This gene encodes a hemopoietic cytokine proposed to signal through a heterodimeric receptor complex composed of the thymic stromal lymphopoietin receptor and the IL-7R alpha chain. It mainly impacts myeloid cells and induces the release of T cell-attracting chemokines from monocytes and enhances the maturation of CD11c(+) dendritic cells. The protein promotes T helper type 2 (TH2) cell responses that are associated with immunity in various inflammatory diseases, including asthma, allergic inflammation and chronic obstructive pulmonary disease. The protein is therefore considered a potential therapeutic target for the treatment of such diseases. In addition, the shorter (predominant) isoform is an antimicrobial protein, displaying antibacterial and antifungal activity against B. cereus, E. coli, E. faecalis, S. mitis, S. epidermidis, and C. albicans. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2020]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSLPNM_033035.5 linkc.410G>A p.Cys137Tyr missense_variant Exon 4 of 4 ENST00000344895.4 NP_149024.1 Q969D9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSLPENST00000344895.4 linkc.410G>A p.Cys137Tyr missense_variant Exon 4 of 4 1 NM_033035.5 ENSP00000339804.3 Q969D9-1
TSLPENST00000420978.6 linkc.410G>A p.Cys137Tyr missense_variant Exon 5 of 5 1 ENSP00000399099.2 A0A0C4DG43
TSLPENST00000379706.4 linkc.122G>A p.Cys41Tyr missense_variant Exon 2 of 2 1 ENSP00000427827.1 Q969D9-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Uncertain
26
DANN
Benign
0.93
DEOGEN2
Uncertain
0.64
.;D;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.56
T;T;T
M_CAP
Benign
0.0088
T
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.97
.;L;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-9.0
D;D;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.68
MutPred
0.58
Loss of methylation at K136 (P = 0.0117);Loss of methylation at K136 (P = 0.0117);.;
MVP
0.16
MPC
1.1
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.95
gMVP
0.62

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: rs140730628; hg19: chr5-110411702; API