NM_019009.4:c.779A>G

Variant names:

• chr11-1277085-T-C
• NM_019009.4:c.779A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_019009.4(TOLLIP):​c.779A>G​(p.Lys260Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TOLLIP NM_019009.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.179
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10234618).
• BP6: Variant 11-1277085-T-C is Benign according to our data. Variant chr11-1277085-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3181097.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019009.4. 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
	TOLLIP	NM_019009.4	MANE Select	c.779A>G	p.Lys260Arg	missense	Exon 6 of 6	NP_061882.2
	TOLLIP	NM_001318512.2		c.629A>G	p.Lys210Arg	missense	Exon 5 of 5	NP_001305441.1	B3KR28
	TOLLIP	NM_001318516.2		c.596A>G	p.Lys199Arg	missense	Exon 5 of 5	NP_001305445.1	F2Z2Y8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP	ENST00000317204.11	TSL:1 MANE Select	c.779A>G	p.Lys260Arg	missense	Exon 6 of 6	ENSP00000314733.5	Q9H0E2-1
	TOLLIP	ENST00000863437.1		c.854A>G	p.Lys285Arg	missense	Exon 7 of 7	ENSP00000533496.1
	TOLLIP	ENST00000961564.1		c.839A>G	p.Lys280Arg	missense	Exon 7 of 7	ENSP00000631623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.99	L
PhyloP100		0.18
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.059
Sift	Benign	0.22	T
Sift4G	Benign	0.15	T
Polyphen		0.017	B
Vest4		0.056
MutPred		0.57		Loss of ubiquitination at K260 (P = 0.0116)
MVP		0.44
MPC		0.41
ClinPred		0.057	T
GERP RS		-2.5
Varity_R		0.041
gMVP		0.39
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

hg19: chr11-1298315;