NM_003823.4:c.255A>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 4P and 3B. PM2PP3_ModerateBP6_ModerateBP7
The NM_003823.4(TNFRSF6B):c.255A>T(p.Leu85Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,014 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L85L) has been classified as Benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TNFRSF6B
NM_003823.4 synonymous
NM_003823.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.41
Publications
25 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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
BayesDel_noAF computational evidence supports a deleterious effect, 0.37
BP6
Variant 20-63697022-A-T is Benign according to our data. Variant chr20-63697022-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1994954.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.41 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003823.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TNFRSF6B | NM_003823.4 | MANE Select | c.255A>T | p.Leu85Leu | synonymous | Exon 1 of 3 | NP_003814.1 | ||
| RTEL1-TNFRSF6B | NR_037882.1 | n.4989A>T | non_coding_transcript_exon | Exon 36 of 38 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TNFRSF6B | ENST00000369996.3 | TSL:1 MANE Select | c.255A>T | p.Leu85Leu | synonymous | Exon 1 of 3 | ENSP00000359013.1 | ||
| RTEL1-TNFRSF6B | ENST00000492259.6 | TSL:5 | n.*1594A>T | non_coding_transcript_exon | Exon 33 of 35 | ENSP00000457428.1 | |||
| RTEL1-TNFRSF6B | ENST00000492259.6 | TSL:5 | n.*1594A>T | 3_prime_UTR | Exon 33 of 35 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456014Hom.: 0 Cov.: 110 AF XY: 0.00 AC XY: 0AN XY: 724576 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1456014
Hom.:
Cov.:
110
AF XY:
AC XY:
0
AN XY:
724576
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44646
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26108
East Asian (EAS)
AF:
AC:
0
AN:
39686
South Asian (SAS)
AF:
AC:
0
AN:
86192
European-Finnish (FIN)
AF:
AC:
0
AN:
48320
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111582
Other (OTH)
AF:
AC:
0
AN:
60248
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Mar 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Pathogenic
DANN
Uncertain
PhyloP100
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
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