Genetic Variant TICAM1:p.Pro365_Pro367dup (chr19-4817276-A-AAGGAGGAGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182919.4(TICAM1):c.1093_1101dupCCTCCTCCT(p.Pro365_Pro367dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,603,266 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TICAM1
NM_182919.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90

Publications

3 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, AD, SD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TICAM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182919.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TICAM1	NM_182919.4	MANE Select	c.1093_1101dupCCTCCTCCT	p.Pro365_Pro367dup	conservative_inframe_insertion	Exon 2 of 2	NP_891549.1	Q8IUC6
TICAM1	NM_001385678.1		c.1051_1059dupCCTCCTCCT	p.Pro351_Pro353dup	conservative_inframe_insertion	Exon 3 of 3	NP_001372607.1
TICAM1	NM_001385679.1		c.958_966dupCCTCCTCCT	p.Pro320_Pro322dup	conservative_inframe_insertion	Exon 2 of 2	NP_001372608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	ENST00000248244.6	TSL:1 MANE Select	c.1093_1101dupCCTCCTCCT	p.Pro365_Pro367dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.1093_1101dupCCTCCTCCT	p.Pro365_Pro367dup	conservative_inframe_insertion	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes

AF:

0.000115

AC:

AN:

147568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1455580

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724162

show subpopulations

African (AFR)

AF:

0.000393

AC:

AN:

33038

American (AMR)

AF:

0.00

AC:

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

85964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00000722

AC:

AN:

1107268

Other (OTH)

AF:

0.0000166

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000115

AC:

AN:

147686

Hom.:

Cov.:

AF XY:

0.0000971

AC XY:

AN XY:

72068

show subpopulations

African (AFR)

AF:

0.000411

AC:

AN:

38964

American (AMR)

AF:

0.00

AC:

AN:

14842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5056

South Asian (SAS)

AF:

0.00

AC:

AN:

4666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67206

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

133

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Herpes simplex encephalitis, susceptibility to, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.9

Mutation Taster

=83/17

polymorphism

(source)

Splicing

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.

19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGGAGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over