Genetic Variant NM_182919.4:c.1959G>A (chr19-4816419-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_182919.4(TICAM1):c.1959G>A(p.Gln653Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,411,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TICAM1
NM_182919.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.611

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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-4816419-C-T is Benign according to our data. Variant chr19-4816419-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3706466.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.611 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TICAM1	NM_182919.4 link	c.1959G>A	p.Gln653Gln	synonymous_variant	Exon 2 of 2	ENST00000248244.6	NP_891549.1	Q8IUC6
TICAM1	NM_001385678.1 link	c.1917G>A	p.Gln639Gln	synonymous_variant	Exon 3 of 3		NP_001372607.1
TICAM1	NM_001385679.1 link	c.1824G>A	p.Gln608Gln	synonymous_variant	Exon 2 of 2		NP_001372608.1
TICAM1	NM_001385680.1 link	c.1317G>A	p.Gln439Gln	synonymous_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.1959G>A	p.Gln653Gln	synonymous_variant	Exon 2 of 2	1	NM_182919.4	ENSP00000248244.4		Q8IUC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000488

AC:

AN:

205088

AF XY:

0.00000913

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1411986

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32054

American (AMR)

AF:

0.00

AC:

AN:

37492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22388

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.00

AC:

AN:

78168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5366

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1088898

Other (OTH)

AF:

0.00

AC:

AN:

58206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 4

Benign:1

Aug 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.43

(source)

DANN

Benign

0.60

PhyloP100

-0.61

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over