19-4816293-C-T

Variant summary

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

The NM_182919.4(TICAM1):​c.2085G>A​(p.Met695Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,523,266 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TICAM1
NM_182919.4 missense

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87
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]

Genome browser will be placed here

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.2085G>A p.Met695Ile missense_variant Exon 2 of 2 ENST00000248244.6 NP_891549.1 Q8IUC6
TICAM1NM_001385678.1 linkc.2043G>A p.Met681Ile missense_variant Exon 3 of 3 NP_001372607.1
TICAM1NM_001385679.1 linkc.1950G>A p.Met650Ile missense_variant Exon 2 of 2 NP_001372608.1
TICAM1NM_001385680.1 linkc.1443G>A p.Met481Ile 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.2085G>A p.Met695Ile missense_variant Exon 2 of 2 1 NM_182919.4 ENSP00000248244.4 Q8IUC6

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000548
AC:
1
AN:
182638
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
96368
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000113
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000292
AC:
4
AN:
1371050
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
672490
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:
0.00000281
Gnomad4 OTH exome
AF:
0.0000177
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000827
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;.
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.69
T;T
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.5
D;.
REVEL
Benign
0.23
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.72
MutPred
0.37
Loss of disorder (P = 0.0411);.;
MVP
0.70
MPC
0.87
ClinPred
0.89
D
GERP RS
4.7
Varity_R
0.86

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: rs778249694; hg19: chr19-4816305; API