3-184376395-A-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001290003.1(THPO):​c.285T>G​(p.Ser95Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S95S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

THPO
NM_001290003.1 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.565
Variant links:
Genes affected
THPO (HGNC:11795): (thrombopoietin) Megakaryocytopoiesis is the cellular development process that leads to platelet production. The main functional protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene. Mutations in this gene are the cause of thrombocythemia 1. Alternative promoter usage and differential splicing result in multiple transcript variants differing in the 5' UTR and/or coding region. Multiple AUG codons upstream of the main open reading frame (ORF) have been identified, and these upstream AUGs inhibit translation of the main ORF at different extent. [provided by RefSeq, Feb 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=0.565 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THPONM_000460.4 linkuse as main transcriptc.-136T>G 5_prime_UTR_variant 2/6 ENST00000647395.1 NP_000451.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THPOENST00000647395.1 linkuse as main transcriptc.-136T>G 5_prime_UTR_variant 2/6 NM_000460.4 ENSP00000494504.1 P40225-1
THPOENST00000445696.6 linkuse as main transcriptc.-136T>G 5_prime_UTR_variant 2/61 ENSP00000410763.2 P40225-2
THPOENST00000645603.2 linkuse as main transcriptc.285T>G p.Ser95Ser synonymous_variant 4/8 ENSP00000494281.2 A0A3B3ITS0
THPOENST00000649095.1 linkuse as main transcriptc.285T>G p.Ser95Ser synonymous_variant 3/7 ENSP00000497904.1 A0A3B3ITS0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
41
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
12
DANN
Benign
0.65

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: rs956732; hg19: chr3-184094183; API