rs1555730283

Positions:

• chr19-4817629-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182919.4(TICAM1):​c.749C>T​(p.Pro250Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TICAM1 NM_182919.4 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 2.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1509983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TICAM1	NM_182919.4	c.749C>T	p.Pro250Leu	missense_variant	2/2	ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1	c.707C>T	p.Pro236Leu	missense_variant	3/3		NP_001372607.1
TICAM1	NM_001385679.1	c.614C>T	p.Pro205Leu	missense_variant	2/2		NP_001372608.1
TICAM1	NM_001385680.1	c.107C>T	p.Pro36Leu	missense_variant	3/3		NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6	c.749C>T	p.Pro250Leu	missense_variant	2/2	1	NM_182919.4	ENSP00000248244.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 4 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.53	D;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.4	D;.
REVEL	Benign	0.097
Sift	Benign	0.24	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.58	P;.
Vest4		0.38
MutPred		0.36		Gain of stability (P = 0.0417);.;
MVP		0.29
MPC		0.59
ClinPred		0.93	D
GERP RS		3.3
Varity_R		0.092

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

Other links and lift over

dbSNP: rs1555730283; hg19: chr19-4817641;