6-73765963-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_133493.5(CD109):c.1141A>T(p.Thr381Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
CD109
NM_133493.5 missense
NM_133493.5 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
CD109 (HGNC:21685): (CD109 molecule) This gene encodes a glycosyl phosphatidylinositol (GPI)-linked glycoprotein that localizes to the surface of platelets, activated T-cells, and endothelial cells. The protein binds to and negatively regulates signalling by transforming growth factor beta (TGF-beta). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.028878152).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD109 | NM_133493.5 | c.1141A>T | p.Thr381Ser | missense_variant | 11/33 | ENST00000287097.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD109 | ENST00000287097.6 | c.1141A>T | p.Thr381Ser | missense_variant | 11/33 | 1 | NM_133493.5 | P1 | |
CD109 | ENST00000437994.6 | c.1141A>T | p.Thr381Ser | missense_variant | 11/33 | 1 | |||
CD109 | ENST00000422508.6 | c.910A>T | p.Thr304Ser | missense_variant | 10/32 | 1 | |||
CD109 | ENST00000649530.1 | n.1113A>T | non_coding_transcript_exon_variant | 10/26 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152194Hom.: 1 Cov.: 31
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?
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250964Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135610
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461718Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727140
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152312Hom.: 1 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74478
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2021 | The c.1141A>T (p.T381S) alteration is located in exon 11 (coding exon 11) of the CD109 gene. This alteration results from a A to T substitution at nucleotide position 1141, causing the threonine (T) at amino acid position 381 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
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;B
Vest4
MutPred
0.25
.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP
MPC
0.034
ClinPred
T
GERP RS
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