rs1554810507

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000373203.9(ENG):​c.396_397delinsAA​(p.Val133Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ENG
ENST00000373203.9 missense

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.162
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENGNM_001114753.3 linkuse as main transcriptc.396_397delinsAA p.Val133Ile missense_variant 4/15 ENST00000373203.9 NP_001108225.1
ENGNM_000118.4 linkuse as main transcriptc.396_397delinsAA p.Val133Ile missense_variant 4/14 NP_000109.1
ENGNM_001406715.1 linkuse as main transcriptc.396_397delinsAA p.Val133Ile missense_variant 4/8 NP_001393644.1
ENGNM_001278138.2 linkuse as main transcriptc.-151_-150delinsAA 5_prime_UTR_variant 4/15 NP_001265067.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENGENST00000373203.9 linkuse as main transcriptc.396_397delinsAA p.Val133Ile missense_variant 4/151 NM_001114753.3 ENSP00000362299 P2P17813-1
ENGENST00000344849.4 linkuse as main transcriptc.396_397delinsAA p.Val133Ile missense_variant 4/141 ENSP00000341917 A2P17813-2
ENGENST00000480266.6 linkuse as main transcriptc.-151_-150delinsAA 5_prime_UTR_variant 4/152 ENSP00000479015
ENGENST00000462196.1 linkuse as main transcriptn.296_297delinsAA non_coding_transcript_exon_variant 3/43

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary hemorrhagic telangiectasia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 26, 2017In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ENG-related disease. This sequence change replaces valine with isoleucine at codon 133 of the ENG protein (p.Val133Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs1554810507; hg19: chr9-130588915; API