rs146354036

Variant names:

• chr11-1277077-C-A
• rs146354036
• NM_019009.4:c.787G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1277077-C-A
• chr11-1277077-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019009.4(TOLLIP):​c.787G>T​(p.Ala263Ser) 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. A263T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TOLLIP NM_019009.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18

Genes affected

TOLLIP (HGNC:16476): (toll interacting protein) This gene encodes a ubiquitin-binding protein that interacts with several Toll-like receptor (TLR) signaling cascade components. The encoded protein regulates inflammatory signaling and is involved in interleukin-1 receptor trafficking and in the turnover of IL1R-associated kinase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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
TOLLIP	NM_019009.4	c.787G>T	p.Ala263Ser	missense_variant	Exon 6 of 6	ENST00000317204.11	NP_061882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOLLIP	ENST00000317204.11	c.787G>T	p.Ala263Ser	missense_variant	Exon 6 of 6	1	NM_019009.4	ENSP00000314733.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.7	L;.;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Benign	0.081	T;T;T;T
Polyphen		1.0	D;.;D;.
Vest4		0.70
MutPred		0.47		Gain of disorder (P = 0.0278);.;.;.;
MVP		0.56
MPC		1.2
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.50

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

Other links and lift over

dbSNP: rs146354036; hg19: chr11-1298307;