rs762635729
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001065.4(TNFRSF1A):c.455G>C(p.Gly152Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,656 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G152E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001065.4 missense
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 |
---|---|---|---|---|---|---|---|
TNFRSF1A | NM_001065.4 | c.455G>C | p.Gly152Ala | missense_variant | 4/10 | ENST00000162749.7 | |
TNFRSF1A | NM_001346091.2 | c.131G>C | p.Gly44Ala | missense_variant | 3/9 | ||
TNFRSF1A | NM_001346092.2 | c.-123G>C | 5_prime_UTR_variant | 4/11 | |||
TNFRSF1A | NR_144351.2 | n.717G>C | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF1A | ENST00000162749.7 | c.455G>C | p.Gly152Ala | missense_variant | 4/10 | 1 | NM_001065.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249896Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135178
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461494Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727036
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
ClinVar
Submissions by phenotype
TNF receptor-associated periodic fever syndrome (TRAPS) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 02, 2019 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces glycine with alanine at codon 152 of the TNFRSF1A protein (p.Gly152Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs762635729, ExAC 0.02%). This variant has not been reported in the literature in individuals with TNFRSF1A-related disease. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at