19-4817645-C-T

Position:

chr19-4817645-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_182919.4(TICAM1):c.733G>A(p.Gly245Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000857 in 1,583,658 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 5 hom. )

Consequence

TICAM1
NM_182919.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.13

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037648976).

BP6

Variant 19-4817645-C-T is Benign according to our data. Variant chr19-4817645-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-4817645-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TICAM1	NM_182919.4 linkuse as main transcript	c.733G>A	p.Gly245Ser	missense_variant	2/2	ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1 linkuse as main transcript	c.691G>A	p.Gly231Ser	missense_variant	3/3		NP_001372607.1
TICAM1	NM_001385679.1 linkuse as main transcript	c.598G>A	p.Gly200Ser	missense_variant	2/2		NP_001372608.1
TICAM1	NM_001385680.1 linkuse as main transcript	c.91G>A	p.Gly31Ser	missense_variant	3/3		NP_001372609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TICAM1	ENST00000248244.6 linkuse as main transcript	c.733G>A	p.Gly245Ser	missense_variant	2/2	1	NM_182919.4	ENSP00000248244	P1

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

414

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00110

AC:

245

AN:

222390

Hom.:

AF XY:

0.000948

AC XY:

114

AN XY:

120266

show subpopulations

Gnomad AFR exome

AF:

0.00716

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000388

Gnomad NFE exome

AF:

0.000506

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000658

AC:

942

AN:

1431452

Hom.:

Cov.:

AF XY:

0.000639

AC XY:

453

AN XY:

709268

show subpopulations

Gnomad4 AFR exome

AF:

0.00684

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000489

Gnomad4 FIN exome

AF:

0.000319

Gnomad4 NFE exome

AF:

0.000448

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00273

AC:

415

AN:

152206

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.00557

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000526

Hom.:

Bravo

AF:

0.00316

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.00105

AC:

127

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	TICAM1: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Herpes simplex encephalitis, susceptibility to, 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0050

DANN

Benign

0.80

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.020

N;.

REVEL

Benign

0.042

Sift

Benign

0.73

T;.

Sift4G

Benign

0.82

T;T

Polyphen

0.017

B;.

Vest4

0.086

MVP

0.22

MPC

0.22

ClinPred

0.0025

GERP RS

-5.1

Varity_R

0.021

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over