chr5-115581066-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021649.7(TICAM2):​c.191G>T​(p.Ser64Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TICAM2
NM_021649.7 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60
Variant links:
Genes affected
TICAM2 (HGNC:21354): (TIR domain containing adaptor molecule 2) Predicted to enable phospholipid binding activity. Involved in several processes, including TRAM-dependent toll-like receptor 4 signaling pathway; regulation of chemokine (C-C motif) ligand 5 production; and regulation of toll-like receptor 4 signaling pathway. Located in endoplasmic reticulum; endosome; and phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]
TMED7-TICAM2 (HGNC:33945): (TMED7-TICAM2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring transmembrane emp24 protein transport domain containing 7 (TMED7) and toll-like receptor adaptor molecule 2 (TICAM2) genes. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. This fusion product functions to negatively regulate the adaptor MyD88-independent toll-like receptor 4 pathway. [provided by RefSeq, Nov 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06493354).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TICAM2NM_021649.7 linkc.191G>T p.Ser64Ile missense_variant Exon 2 of 2 ENST00000427199.3 NP_067681.1 Q86XR7-1
TMED7-TICAM2NM_001164468.4 linkc.698G>T p.Ser233Ile missense_variant Exon 4 of 4 NP_001157940.1 Q86XR7-2
TMED7-TICAM2NM_001164469.4 linkc.*249G>T 3_prime_UTR_variant Exon 4 of 4 NP_001157941.1 Q86XR7Q9Y3B3-2A0A0A6YYA0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TICAM2ENST00000427199.3 linkc.191G>T p.Ser64Ile missense_variant Exon 2 of 2 1 NM_021649.7 ENSP00000415139.3 Q86XR7-1
TMED7-TICAM2ENST00000282382.8 linkc.698G>T p.Ser233Ile missense_variant Exon 4 of 4 2 ENSP00000282382.4
TMED7-TICAM2ENST00000333314 linkc.*249G>T 3_prime_UTR_variant Exon 4 of 4 2 ENSP00000333650.3 A0A0A6YYA0
TMED7-TICAM2ENST00000514548.1 linkn.497G>T non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.33
DANN
Benign
0.96
DEOGEN2
Benign
0.087
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.34
T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.13
N;N
REVEL
Benign
0.0090
Sift
Benign
0.051
T;T
Sift4G
Benign
0.075
T;T
Polyphen
0.0050
.;B
Vest4
0.078
MutPred
0.28
.;Loss of phosphorylation at S64 (P = 0.012);
MVP
0.12
MPC
0.99
ClinPred
0.13
T
GERP RS
-0.31
Varity_R
0.043
gMVP
0.32

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.

Other links and lift over

dbSNP: rs113049216; hg19: chr5-114916763; API