Genetic Variant NM_182919.4:c.2050G>T (chr19-4816328-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34

Publications

0 publications found

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]

TICAM1 Gene-Disease associations (from GenCC):

herpes simplex encephalitis, susceptibility to, 4
Inheritance: AR, SD, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TICAM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
TICAM1	NM_182919.4 link	c.2050G>T	p.Ala684Ser	missense_variant	Exon 2 of 2	ENST00000248244.6	NP_891549.1	Q8IUC6
TICAM1	NM_001385678.1 link	c.2008G>T	p.Ala670Ser	missense_variant	Exon 3 of 3		NP_001372607.1
TICAM1	NM_001385679.1 link	c.1915G>T	p.Ala639Ser	missense_variant	Exon 2 of 2		NP_001372608.1
TICAM1	NM_001385680.1 link	c.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
TICAM1	ENST00000248244.6 link	c.2050G>T	p.Ala684Ser	missense_variant	Exon 2 of 2	1	NM_182919.4	ENSP00000248244.4		Q8IUC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705070

African (AFR)

AF:

0.00

AC:

AN:

32046

American (AMR)

AF:

0.00

AC:

AN:

37616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23212

East Asian (EAS)

AF:

0.00

AC:

AN:

39444

South Asian (SAS)

AF:

0.00

AC:

AN:

80256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094298

Other (OTH)

AF:

0.00

AC:

AN:

58736

GnomAD4 genome

Cov.:

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

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.0

L;.

PhyloP100

4.3

PrimateAI

Uncertain

0.63

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

GERP RS

4.7

Varity_R

0.46

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over