rs869025565
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004425.4(ECM1):c.507del(p.Arg171GlyfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ECM1
NM_004425.4 frameshift
NM_004425.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.62
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 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-150510996-CT-C is Pathogenic according to our data. Variant chr1-150510996-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 222947.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECM1 | NM_004425.4 | c.507del | p.Arg171GlyfsTer7 | frameshift_variant | 6/10 | ENST00000369047.9 | |
ECM1 | NM_001202858.2 | c.588del | p.Arg198GlyfsTer7 | frameshift_variant | 6/10 | ||
ECM1 | NM_022664.3 | c.507del | p.Arg171GlyfsTer7 | frameshift_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECM1 | ENST00000369047.9 | c.507del | p.Arg171GlyfsTer7 | frameshift_variant | 6/10 | 1 | NM_004425.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251308Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135868
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461866Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727228
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lipid proteinosis Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2003 | - - |
ECM1-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2023 | The ECM1 c.507delT variant is predicted to result in a frameshift and premature protein termination (p.Arg171Glyfs*7). This variant has been reported in the homozygous state in individuals with lipoid proteinosis (Hamada et al. 2003. PubMed ID: 12603844; Samdani et al. 2010. PubMed ID: 21886756; Oguz Akarsu et al. 2018. PubMed ID: 28434238). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-150483472-CT-C). Frameshift variants in ECM1 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at