19-4817276-AAGGAGGAGGAGG-AAGGAGGAGGAGGAGGAGG

Variant names:

• chr19-4817276-A-AAGGAGG
• rs11466722
• NM_182919.4:c.1096_1101dupCCTCCT

Variant summary

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

The NM_182919.4(TICAM1):​c.1096_1101dupCCTCCT​(p.Pro366_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 0.000129 in 1,603,262 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: TICAM1 NM_182919.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.90
• Publications: 3 publications found

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)

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TICAM1	NM_182919.4	MANE Select	c.1096_1101dupCCTCCT	p.Pro366_Pro367dup	conservative_inframe_insertion	Exon 2 of 2	NP_891549.1	Q8IUC6
	TICAM1	NM_001385678.1		c.1054_1059dupCCTCCT	p.Pro352_Pro353dup	conservative_inframe_insertion	Exon 3 of 3	NP_001372607.1
	TICAM1	NM_001385679.1		c.961_966dupCCTCCT	p.Pro321_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.1096_1101dupCCTCCT	p.Pro366_Pro367dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000248244.4	Q8IUC6
	TICAM1	ENST00000868535.1		c.1096_1101dupCCTCCT	p.Pro366_Pro367dup	conservative_inframe_insertion	Exon 3 of 3	ENSP00000538594.1

Frequencies

GnomAD3 genomes AF: 0.000278 AC: 41 AN: 147566 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000264 AC: 65 AN: 246324 AF XY: 0.000247

Gnomad AFR exome AF: 0.000322

Gnomad AMR exome AF: 0.000967

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000112 AC: 163 AN: 1455578 Hom.: 0 Cov.: 61 AF XY: 0.000112 AC XY: 81 AN XY: 724160

African (AFR) AF: 0.000363 AC: 12 AN: 33038

American (AMR) AF: 0.000807 AC: 36 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39650

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00194 AC: 11 AN: 5674

European-Non Finnish (NFE) AF: 0.0000713 AC: 79 AN: 1107266

Other (OTH) AF: 0.000183 AC: 11 AN: 60102

GnomAD4 genome AF: 0.000298 AC: 44 AN: 147684 Hom.: 0 Cov.: 27 AF XY: 0.000375 AC XY: 27 AN XY: 72066

African (AFR) AF: 0.000334 AC: 13 AN: 38964

American (AMR) AF: 0.00135 AC: 20 AN: 14840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5056

South Asian (SAS) AF: 0.00 AC: 0 AN: 4666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10266

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000134 AC: 9 AN: 67206

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.0000840 Hom.: 133

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11466722; hg19: chr19-4817288;