NM_003823.4:c.56C>T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003823.4(TNFRSF6B):c.56C>T(p.Pro19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,520 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19S) has been classified as Uncertain significance.
Frequency
Consequence
NM_003823.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNFRSF6B | ENST00000369996.3 | c.56C>T | p.Pro19Leu | missense_variant | Exon 1 of 3 | 1 | NM_003823.4 | ENSP00000359013.1 | ||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*1395C>T | non_coding_transcript_exon_variant | Exon 33 of 35 | 5 | ENSP00000457428.1 | ||||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*1395C>T | 3_prime_UTR_variant | Exon 33 of 35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000425 AC: 1AN: 235122Hom.: 0 AF XY: 0.00000775 AC XY: 1AN XY: 128974
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1457520Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 724812
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 19 of the TNFRSF6B protein (p.Pro19Leu). This variant is present in population databases (rs763121875, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with TNFRSF6B-related conditions. 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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