20-63696823-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003823.4(TNFRSF6B):c.56C>G(p.Pro19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,609,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
TNFRSF6B
NM_003823.4 missense
NM_003823.4 missense
Scores
2
17
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.38
Publications
0 publications found
Genes affected
TNFRSF6B (HGNC:11921): (TNF receptor superfamily member 6b) This gene belongs to the tumor necrosis factor receptor superfamily. The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript. [provided by RefSeq, Feb 2011]
RTEL1-TNFRSF6B (HGNC:44095): (RTEL1-TNFRSF6B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RTEL1 (regulator of telomere elongation helicase 1) and TNFRSF6B (tumor necrosis factor receptor superfamily, member 6b, decoy) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19707656).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TNFRSF6B | ENST00000369996.3 | c.56C>G | p.Pro19Arg | missense_variant | Exon 1 of 3 | 1 | NM_003823.4 | ENSP00000359013.1 | ||
| RTEL1-TNFRSF6B | ENST00000492259.6 | n.*1395C>G | non_coding_transcript_exon_variant | Exon 33 of 35 | 5 | ENSP00000457428.1 | ||||
| RTEL1-TNFRSF6B | ENST00000492259.6 | n.*1395C>G | 3_prime_UTR_variant | Exon 33 of 35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152224
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457520Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724812 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1457520
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
724812
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33426
American (AMR)
AF:
AC:
0
AN:
44490
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25994
East Asian (EAS)
AF:
AC:
0
AN:
39638
South Asian (SAS)
AF:
AC:
1
AN:
85728
European-Finnish (FIN)
AF:
AC:
0
AN:
51634
Middle Eastern (MID)
AF:
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1110722
Other (OTH)
AF:
AC:
0
AN:
60134
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74372 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152224
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
74372
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41468
American (AMR)
AF:
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
1
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68022
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of helix (P = 0.0082);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.