rs780770024
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PVS1PM2BP6
The NM_000243.3(MEFV):c.1780C>T(p.Gln594Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,800 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q594Q) has been classified as Likely benign.
Frequency
Consequence
NM_000243.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEFV | NM_000243.3 | c.1780C>T | p.Gln594Ter | stop_gained | 9/10 | ENST00000219596.6 | |
MEFV | NM_001198536.2 | c.1322C>T | p.Ser441Leu | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEFV | ENST00000219596.6 | c.1780C>T | p.Gln594Ter | stop_gained | 9/10 | 1 | NM_000243.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251084Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135792
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461662Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727108
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Familial Mediterranean fever Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 527802). This variant has not been reported in the literature in individuals affected with MEFV-related conditions. This variant is present in population databases (rs780770024, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln594*) in the MEFV gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 188 amino acid(s) of the MEFV protein. - |
Familial Mediterranean fever;C0085077:Acute febrile neutrophilic dermatosis;C1851347:Familial Mediterranean fever, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 20, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2021 | - - |
Acute febrile neutrophilic dermatosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Familial Mediterranean fever, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at