rs727502791
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 10P and 4B. PVS1_ModeratePP5_Very_StrongBS2
The NM_003480.4(MFAP5):c.472C>T(p.Arg158Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R158R) has been classified as Likely benign.
Frequency
Consequence
NM_003480.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFAP5 | NM_003480.4 | c.472C>T | p.Arg158Ter | stop_gained | 10/10 | ENST00000359478.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFAP5 | ENST00000359478.7 | c.472C>T | p.Arg158Ter | stop_gained | 10/10 | 1 | NM_003480.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251418Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135896
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461746Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 727176
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 9 Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Jul 27, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Arcensus | Feb 01, 2013 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 04, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10% (PVS1_S). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:25434006, PS3_S). The variant has been reported to be associated with MFAP5 related disorder (ClinVar ID: VCV000162199, PMID:25434006).Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
Isolated thoracic aortic aneurysm Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Department of Vascular Biology, Beijing Anzhen Hospital | Sep 01, 2018 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 05, 2023 | Experimental studies have shown that this premature translational stop signal affects MFAP5 function (PMID: 25434006). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 162199). This premature translational stop signal has been observed in individuals with MFAP5-related conditions (PMID: 25434006, 33824467). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs727502791, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Arg158*) in the MFAP5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the MFAP5 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at