6-47284159-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014452.5(TNFRSF21):ā€‹c.1022A>Gā€‹(p.His341Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

TNFRSF21
NM_014452.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46
Variant links:
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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNFRSF21NM_014452.5 linkuse as main transcriptc.1022A>G p.His341Arg missense_variant 3/6 ENST00000296861.2 NP_055267.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNFRSF21ENST00000296861.2 linkuse as main transcriptc.1022A>G p.His341Arg missense_variant 3/61 NM_014452.5 ENSP00000296861 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000636
AC:
16
AN:
251380
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000968
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.0000344
AC XY:
25
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 24, 2022The c.1022A>G (p.H341R) alteration is located in exon 3 (coding exon 3) of the TNFRSF21 gene. This alteration results from a A to G substitution at nucleotide position 1022, causing the histidine (H) at amino acid position 341 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.35
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.11
T
Polyphen
0.045
B
Vest4
0.68
MutPred
0.31
Gain of MoRF binding (P = 0.0101);
MVP
0.80
MPC
0.97
ClinPred
0.15
T
GERP RS
5.9
Varity_R
0.32
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775155357; hg19: chr6-47251895; API