NM_014452.5:c.1622C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_014452.5(TNFRSF21):c.1622C>T(p.Ser541Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,598,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
TNFRSF21
NM_014452.5 missense
NM_014452.5 missense
Scores
4
11
4
Clinical Significance
Conservation
PhyloP100: 9.64
Publications
0 publications found
Genes affected
TNFRSF21 (HGNC:13469): (TNF receptor superfamily member 21) This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TNFRSF21 | NM_014452.5 | c.1622C>T | p.Ser541Phe | missense_variant | Exon 5 of 6 | ENST00000296861.2 | NP_055267.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
152152
Hom.:
Cov.:
32
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: 6.92e-7 AC: 1AN: 1446088Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 718754 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1446088
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
718754
show subpopulations
African (AFR)
AF:
AC:
1
AN:
32470
American (AMR)
AF:
AC:
0
AN:
41394
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25714
East Asian (EAS)
AF:
AC:
0
AN:
38668
South Asian (SAS)
AF:
AC:
0
AN:
83078
European-Finnish (FIN)
AF:
AC:
0
AN:
53206
Middle Eastern (MID)
AF:
AC:
0
AN:
5468
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106316
Other (OTH)
AF:
AC:
0
AN:
59774
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 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
152152
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74318
show subpopulations
African (AFR)
AF:
AC:
3
AN:
41426
American (AMR)
AF:
AC:
1
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68032
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.538
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.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jan 23, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1622C>T (p.S541F) alteration is located in exon 5 (coding exon 5) of the TNFRSF21 gene. This alteration results from a C to T substitution at nucleotide position 1622, causing the serine (S) at amino acid position 541 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of phosphorylation at S541 (P = 0.0485);
MVP
MPC
ClinPred
D
GERP RS
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
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