1-150509696-C-T
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
Consequence
NM_004425.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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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 AF: 0.0000197 AC: 3AN: 151948Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251476Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135906
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461696Hom.: 1 Cov.: 49 AF XY: 0.0000193 AC XY: 14AN XY: 727148
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151948Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74216
ClinVar
Submissions by phenotype
Lipid proteinosis Pathogenic:3
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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. -
not provided Pathogenic:2
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) -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at