rs104895288

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001065.4(TNFRSF1A):​c.434A>T​(p.Asn145Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TNFRSF1A
NM_001065.4 missense

Scores

3
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55
Variant links:
Genes affected
TNFRSF1A (HGNC:11916): (TNF receptor superfamily member 1A) This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity TNR1A_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNFRSF1ANM_001065.4 linkc.434A>T p.Asn145Ile missense_variant Exon 4 of 10 ENST00000162749.7 NP_001056.1 P19438-1
TNFRSF1ANM_001346091.2 linkc.110A>T p.Asn37Ile missense_variant Exon 3 of 9 NP_001333020.1 P19438-2J9PH39
TNFRSF1ANM_001346092.2 linkc.-144A>T 5_prime_UTR_variant Exon 4 of 11 NP_001333021.1 P19438
TNFRSF1ANR_144351.2 linkn.696A>T non_coding_transcript_exon_variant Exon 4 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNFRSF1AENST00000162749.7 linkc.434A>T p.Asn145Ile missense_variant Exon 4 of 10 1 NM_001065.4 ENSP00000162749.2 P19438-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461720
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.59
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.84
D;D;D;.;T
Eigen
Benign
0.046
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.81
T;T;T;T;T
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.61
D;D;D;D;D
MetaSVM
Uncertain
0.10
D
MutationAssessor
Benign
1.7
L;.;.;L;.
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-5.3
D;D;D;D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;.;D;.
Polyphen
1.0
D;D;.;.;.
Vest4
0.64
MutPred
0.50
Gain of catalytic residue at L150 (P = 0);.;Gain of catalytic residue at L150 (P = 0);Gain of catalytic residue at L150 (P = 0);Gain of catalytic residue at L150 (P = 0);
MVP
0.92
MPC
1.6
ClinPred
0.99
D
GERP RS
0.93
Varity_R
0.76
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-6442571; API