rs201218843

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659
Variant links:
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]

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ACMG classification

Classification made for transcript

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
TIGITNM_173799.4 linkc.434C>A p.Ala145Asp missense_variant Exon 3 of 4 ENST00000383671.8 NP_776160.2 Q495A1-1
TIGITXM_047447671.1 linkc.434C>A p.Ala145Asp missense_variant Exon 3 of 4 XP_047303627.1
TIGITXM_047447672.1 linkc.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
TIGITENST00000383671.8 linkc.434C>A p.Ala145Asp missense_variant Exon 3 of 4 1 NM_173799.4 ENSP00000373167.3 Q495A1-1

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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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