rs138250796

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003246.4(THBS1):​c.597C>G​(p.Ile199Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

THBS1
NM_003246.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18102342).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
THBS1NM_003246.4 linkc.597C>G p.Ile199Met missense_variant Exon 3 of 22 ENST00000260356.6 NP_003237.2 P07996-1
THBS1XM_047432980.1 linkc.597C>G p.Ile199Met missense_variant Exon 3 of 22 XP_047288936.1
THBS1XM_011521971.3 linkc.597C>G p.Ile199Met missense_variant Exon 3 of 21 XP_011520273.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
THBS1ENST00000260356.6 linkc.597C>G p.Ile199Met missense_variant Exon 3 of 22 1 NM_003246.4 ENSP00000260356.5 P07996-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460130
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726302
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.082
N
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.84
N
REVEL
Benign
0.080
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.35
B
Vest4
0.42
MutPred
0.40
Gain of methylation at R198 (P = 0.0444);
MVP
0.19
MPC
0.91
ClinPred
0.48
T
GERP RS
-5.1
Varity_R
0.43
gMVP
0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-39874923; API