rs371087831

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003820.4(TNFRSF14):​c.785C>A​(p.Pro262Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. P262L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TNFRSF14
NM_003820.4 missense

Scores

3
2
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.464
Variant links:
Genes affected
TNFRSF14 (HGNC:11912): (TNF receptor superfamily member 14) This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32430398).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNFRSF14NM_003820.4 linkuse as main transcriptc.785C>A p.Pro262Gln missense_variant 8/8 ENST00000355716.5 NP_003811.2 Q92956-1A0A024R052

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNFRSF14ENST00000355716.5 linkuse as main transcriptc.785C>A p.Pro262Gln missense_variant 8/81 NM_003820.4 ENSP00000347948.4 Q92956-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250402
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135658
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461154
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726858
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.034
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.24
T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.081
N
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.29
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.14
MutPred
0.29
Loss of catalytic residue at P261 (P = 0.0151);
MVP
0.39
MPC
0.57
ClinPred
0.63
D
GERP RS
2.0
Varity_R
0.089
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs371087831; hg19: chr1-2494645; API