chr3-114299597-T-A

Position:

• chr3-114299597-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173799.4(TIGIT):​c.392T>A​(p.Val131Glu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIGIT NM_173799.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001117
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.16

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08523348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIGIT	NM_173799.4	c.392T>A	p.Val131Glu	missense_variant, splice_region_variant	3/4	ENST00000383671.8	NP_776160.2
TIGIT	XM_047447671.1	c.392T>A	p.Val131Glu	missense_variant, splice_region_variant	3/4		XP_047303627.1
TIGIT	XM_047447672.1	c.29T>A	p.Val10Glu	missense_variant, splice_region_variant	2/3		XP_047303628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIGIT	ENST00000383671.8	c.392T>A	p.Val131Glu	missense_variant, splice_region_variant	3/4	1	NM_173799.4	ENSP00000373167	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.392T>A (p.V131E) alteration is located in exon 3 (coding exon 3) of the TIGIT gene. This alteration results from a T to A substitution at nucleotide position 392, causing the valine (V) at amino acid position 131 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	4.4
DANN	Benign	0.94
DEOGEN2	Benign	0.014	T;.;T;T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.59	T;T;.;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.085	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;.;M;M;.
MutationTaster	Benign	0.76	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.93	N;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.022	D;D;T;T;D
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.0	.;.;B;B;.
Vest4		0.28, 0.26, 0.26
MutPred		0.36		.;.;Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);.;
MVP		0.35
MPC		0.17
ClinPred		0.069	T
GERP RS		-3.0
Varity_R		0.34
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.052
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-114018444;