chr15-39585503-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2
The NM_003246.4(THBS1):c.1060C>T(p.Pro354Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000917 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000092 ( 0 hom. )
Consequence
THBS1
NM_003246.4 missense
NM_003246.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.17
Genes affected
THBS1 (HGNC:11785): (thrombospondin 1) The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP5
Variant 15-39585503-C-T is Pathogenic according to our data. Variant chr15-39585503-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 929776.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBS1 | NM_003246.4 | c.1060C>T | p.Pro354Ser | missense_variant | 7/22 | ENST00000260356.6 | |
THBS1 | XM_047432980.1 | c.1060C>T | p.Pro354Ser | missense_variant | 7/22 | ||
THBS1 | XM_011521971.3 | c.1060C>T | p.Pro354Ser | missense_variant | 7/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBS1 | ENST00000260356.6 | c.1060C>T | p.Pro354Ser | missense_variant | 7/22 | 1 | NM_003246.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000255 AC: 64AN: 251456Hom.: 0 AF XY: 0.000235 AC XY: 32AN XY: 135902
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GnomAD4 exome AF: 0.0000917 AC: 134AN: 1461840Hom.: 0 Cov.: 30 AF XY: 0.0000949 AC XY: 69AN XY: 727228
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74494
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Premature ovarian failure Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano | Mar 02, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.1060C>T (p.P354S) alteration is located in exon 7 (coding exon 6) of the THBS1 gene. This alteration results from a C to T substitution at nucleotide position 1060, causing the proline (P) at amino acid position 354 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at