rs201218843

Variant names:

• chr3-114299639-C-A
• rs201218843
• NM_173799.4:c.434C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-114299639-C-A
• chr3-114299639-C-T

Variant summary

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

The NM_173799.4(TIGIT):​c.434C>A​(p.Ala145Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A145V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TIGIT NM_173799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659

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=0.22202918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGIT	NM_173799.4	c.434C>A	p.Ala145Asp	missense_variant	Exon 3 of 4	ENST00000383671.8	NP_776160.2
TIGIT	XM_047447671.1	c.434C>A	p.Ala145Asp	missense_variant	Exon 3 of 4		XP_047303627.1
TIGIT	XM_047447672.1	c.71C>A	p.Ala24Asp	missense_variant	Exon 2 of 3		XP_047303628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGIT	ENST00000383671.8	c.434C>A	p.Ala145Asp	missense_variant	Exon 3 of 4	1	NM_173799.4	ENSP00000373167.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461080 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.;T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.66	T;T;.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;.;M;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D
Polyphen		0.99	.;.;D;D;.
Vest4		0.94, 0.94, 0.94
MutPred		0.60		.;.;Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);.;
MVP		0.57
MPC		0.59
ClinPred		0.55	D
GERP RS		1.6
Varity_R		0.23
gMVP		0.61

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: rs201218843; hg19: chr3-114018486; COSMIC: COSV67328936; COSMIC: COSV67328936;