rs151306047
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000243.3(MEFV):āc.311C>Gā(p.Ser104Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000243.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEFV | NM_000243.3 | c.311C>G | p.Ser104Cys | missense_variant | 2/10 | ENST00000219596.6 | |
MEFV | NM_001198536.2 | c.277+1554C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEFV | ENST00000219596.6 | c.311C>G | p.Ser104Cys | missense_variant | 2/10 | 1 | NM_000243.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152266Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246732Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134572
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460362Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0AN XY: 726506
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152266Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74392
ClinVar
Submissions by phenotype
Familial Mediterranean fever Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 28, 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 578339). This missense change has been observed in individual(s) with clinical features of familial Mediterranean fever (PMID: 31989427, 32199921). This variant is present in population databases (rs151306047, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 104 of the MEFV protein (p.Ser104Cys). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
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 | Dec 15, 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