rs376421303

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182919.4(TICAM1):​c.2050G>T​(p.Ala684Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A684T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TICAM1
NM_182919.4 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34
Variant links:
Genes affected
TICAM1 (HGNC:18348): (TIR domain containing adaptor molecule 1) This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. This protein is involved in native immunity against invading pathogens. It specifically interacts with toll-like receptor 3, but not with other TLRs, and this association mediates dsRNA induction of interferon-beta through activation of nuclear factor kappa-B, during an antiviral immune response. Mutations in this gene are associated with encephalopathy, acute, infection-induced. [provided by RefSeq, Jul 2020]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
TICAM1NM_182919.4 linkc.2050G>T p.Ala684Ser missense_variant Exon 2 of 2 ENST00000248244.6 NP_891549.1 Q8IUC6
TICAM1NM_001385678.1 linkc.2008G>T p.Ala670Ser missense_variant Exon 3 of 3 NP_001372607.1
TICAM1NM_001385679.1 linkc.1915G>T p.Ala639Ser missense_variant Exon 2 of 2 NP_001372608.1
TICAM1NM_001385680.1 linkc.1408G>T p.Ala470Ser missense_variant Exon 3 of 3 NP_001372609.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TICAM1ENST00000248244.6 linkc.2050G>T p.Ala684Ser missense_variant Exon 2 of 2 1 NM_182919.4 ENSP00000248244.4 Q8IUC6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1422836
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
705070
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:
0.00
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
Uncertain
0.48
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.084
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.9
N;.
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.65
MutPred
0.55
Gain of sheet (P = 0.0827);.;
MVP
0.60
MPC
0.79
ClinPred
0.97
D
GERP RS
4.7
Varity_R
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chr19-4816340; API