3-114295869-G-C

Variant names:

• chr3-114295869-G-C
• rs201068475
• NM_173799.4:c.386G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173799.4(TIGIT):​c.386G>C​(p.Ser129Thr) 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. 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. S129I) 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: 0.121
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10579911).

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.386G>C	p.Ser129Thr	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.386G>C	p.Ser129Thr	missense	Exon 2 of 4	ENSP00000373167.3	Q495A1-1
	TIGIT	ENST00000481065.5	TSL:2	c.587G>C	p.Ser196Thr	missense	Exon 3 of 5	ENSP00000420552.1	A0A0C4DGA4
	TIGIT	ENST00000486257.5	TSL:5	c.386G>C	p.Ser129Thr	missense	Exon 3 of 5	ENSP00000419085.1	Q495A1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.12
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.015
Sift	Benign	0.090	T
Sift4G	Benign	0.079	T
Polyphen		0.017	B
Vest4		0.19
MutPred		0.34		Loss of disorder (P = 0.0565)
MVP		0.50
MPC		0.12
ClinPred		0.052	T
GERP RS		0.94
Varity_R		0.18
gMVP		0.28
Mutation Taster		=97/3	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

dbSNP: rs201068475; hg19: chr3-114014716;