rs376421303

Variant names:

• chr19-4816328-C-A
• NM_182919.4:c.2050G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-4816328-C-A
• chr19-4816328-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	c.2050G>T	p.Ala684Ser	missense_variant	Exon 2 of 2	ENST00000248244.6	NP_891549.1
TICAM1	NM_001385678.1	c.2008G>T	p.Ala670Ser	missense_variant	Exon 3 of 3		NP_001372607.1
TICAM1	NM_001385679.1	c.1915G>T	p.Ala639Ser	missense_variant	Exon 2 of 2		NP_001372608.1
TICAM1	NM_001385680.1	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	c.2050G>T	p.Ala684Ser	missense_variant	Exon 2 of 2	1	NM_182919.4	ENSP00000248244.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422836 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 705070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.63	T
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	D
GERP RS		4.7
Varity_R		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4816340;