Genetic Variant TSLP:p.Cys90Tyr (chr5-111073563-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_033035.5(TSLP):c.269G>A(p.Cys90Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

Publications

0 publications found

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]

TSLP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033035.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSLP	NM_033035.5	MANE Select	c.269G>A	p.Cys90Tyr	missense	Exon 3 of 4	NP_149024.1
TSLP	NR_045089.2		n.1691G>A		non_coding_transcript_exon	Exon 4 of 5
TSLP	NM_138551.5		c.-20G>A		5_prime_UTR	Exon 1 of 2	NP_612561.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TSLP	ENST00000344895.4	TSL:1 MANE Select	c.269G>A	p.Cys90Tyr	missense	Exon 3 of 4	ENSP00000339804.3
TSLP	ENST00000420978.6	TSL:1	c.269G>A	p.Cys90Tyr	missense	Exon 4 of 5	ENSP00000399099.2
TSLP	ENST00000379706.4	TSL:1	c.-20G>A		5_prime_UTR	Exon 1 of 2	ENSP00000427827.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.97

PhyloP100

2.7

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.50

MutPred

0.63

Loss of catalytic residue at S92 (P = 0.0794)

MVP

0.13

MPC

1.1

ClinPred

1.0

GERP RS

4.3

PromoterAI

0.036

Neutral

(source)

Varity_R

0.96

gMVP

0.63

Mutation Taster

=261/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over