rs201219748

Variant names:

• chr3-114295833-C-G
• rs201219748
• NM_173799.4:c.350C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-114295833-C-G
• chr3-114295833-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173799.4(TIGIT):​c.350C>G​(p.Thr117Arg) 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. 14/24 in silico tools predict a benign outcome for this variant. 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. T117M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIGIT NM_173799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

Genes affected

TIGIT (HGNC:26838): (T cell immunoreceptor with Ig and ITIM domains) This gene encodes a member of the PVR (poliovirus receptor) family of immunoglobin proteins. The product of this gene is expressed on several classes of T cells including follicular B helper T cells (TFH). The protein has been shown to bind PVR with high affinity; this binding is thought to assist interactions between TFH and dendritic cells to regulate T cell dependent B cell responses.[provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173799.4. 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
	TIGIT	NM_173799.4	MANE Select	c.350C>G	p.Thr117Arg	missense	Exon 2 of 4	NP_776160.2	Q495A1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGIT	ENST00000383671.8	TSL:1 MANE Select	c.350C>G	p.Thr117Arg	missense	Exon 2 of 4	ENSP00000373167.3	Q495A1-1
	TIGIT	ENST00000481065.5	TSL:2	c.551C>G	p.Thr184Arg	missense	Exon 3 of 5	ENSP00000420552.1	A0A0C4DGA4
	TIGIT	ENST00000486257.5	TSL:5	c.350C>G	p.Thr117Arg	missense	Exon 3 of 5	ENSP00000419085.1	Q495A1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.13
Sift	Benign	0.054	T
Sift4G	Uncertain	0.011	D
Polyphen		0.89	P
Vest4		0.27
MutPred		0.55		Gain of solvent accessibility (P = 0.0456)
MVP		0.58
MPC		0.33
ClinPred		0.78	D
GERP RS		3.6
Varity_R		0.42
gMVP		0.52
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.28		Position offset: 41

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

Other links and lift over

dbSNP: rs201219748; hg19: chr3-114014680;