9-127825349-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001114753.3(ENG):c.698C>A(p.Thr233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T233T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 26)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ENG
NM_001114753.3 missense
NM_001114753.3 missense
Scores
11
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.74
Genes affected
ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a region_of_interest OR1, C-terminal part (size 130) in uniprot entity EGLN_HUMAN there are 10 pathogenic changes around while only 4 benign (71%) in NM_001114753.3
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.698C>A | p.Thr233Lys | missense_variant | Exon 6 of 15 | ENST00000373203.9 | NP_001108225.1 | |
ENG | NM_000118.4 | c.698C>A | p.Thr233Lys | missense_variant | Exon 6 of 14 | NP_000109.1 | ||
ENG | NM_001278138.2 | c.152C>A | p.Thr51Lys | missense_variant | Exon 6 of 15 | NP_001265067.1 | ||
ENG | NM_001406715.1 | c.698C>A | p.Thr233Lys | missense_variant | Exon 6 of 8 | NP_001393644.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.698C>A | p.Thr233Lys | missense_variant | Exon 6 of 15 | 1 | NM_001114753.3 | ENSP00000362299.4 | ||
ENG | ENST00000344849.4 | c.698C>A | p.Thr233Lys | missense_variant | Exon 6 of 14 | 1 | ENSP00000341917.3 | |||
ENG | ENST00000480266.6 | c.152C>A | p.Thr51Lys | missense_variant | Exon 6 of 15 | 2 | ENSP00000479015.1 |
Frequencies
GnomAD3 genomes Cov.: 26
GnomAD3 genomes
Cov.:
26
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460412Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726508
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1460412
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
726508
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 26
GnomAD4 genome
Cov.:
26
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of methylation at T233 (P = 0.0152);.;Gain of methylation at T233 (P = 0.0152);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at