1-150509696-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004425.4(ECM1):c.157C>T(p.Arg53*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,644 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 1 hom. )
Consequence
ECM1
NM_004425.4 stop_gained
NM_004425.4 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 0.0850
Genes affected
ECM1 (HGNC:3153): (extracellular matrix protein 1) This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-150509696-C-T is Pathogenic according to our data. Variant chr1-150509696-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 7475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ECM1 | NM_004425.4 | c.157C>T | p.Arg53* | stop_gained | Exon 3 of 10 | ENST00000369047.9 | NP_004416.2 | |
| ECM1 | NM_001202858.2 | c.157C>T | p.Arg53* | stop_gained | Exon 3 of 10 | NP_001189787.1 | ||
| ECM1 | NM_022664.3 | c.157C>T | p.Arg53* | stop_gained | Exon 3 of 9 | NP_073155.2 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 151948Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251476Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135906
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461696Hom.: 1 Cov.: 49 AF XY: 0.0000193 AC XY: 14AN XY: 727148
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GnomAD4 genome 0.0000197 AC: 3AN: 151948Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74216
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Lipid proteinosis Pathogenic:3
| Pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The stop-gained variant c.157C>T (p.Arg53Ter) in the ECM1 gene has been reported in the homozygous state in individuals affected with lipoid proteinosis (Nasir et al., 2011; Akoglu et al., 2011). This variant is reported with the allele frequency (0.004%) in the gnomAD Exomes and novel (not in any individuals) in 1000 Genomes. It has been submitted to ClinVar as Pathogenic. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed. - |
| Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2003 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Pathogenic:2
| Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2024 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: Sercu2009[Review], Oyama2013[Review], 25525159, 17199583, 25819081, 12603844, 34426522, 31589614, Wu2019[article], 21791056, 31896839, 17927570, 20666665) - |
| Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
Vest4
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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