3-171066609-C-T

Variant summary

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

The NM_015028.4(TNIK):​c.3826G>A​(p.Val1276Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TNIK
NM_015028.4 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
TNIK (HGNC:30765): (TRAF2 and NCK interacting kinase) Wnt signaling plays important roles in carcinogenesis and embryonic development. The protein encoded by this gene is a serine/threonine kinase that functions as an activator of the Wnt signaling pathway. Mutations in this gene are associated with an autosomal recessive form of cognitive disability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNIKNM_015028.4 linkc.3826G>A p.Val1276Met missense_variant Exon 31 of 33 ENST00000436636.7 NP_055843.1 Q9UKE5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNIKENST00000436636.7 linkc.3826G>A p.Val1276Met missense_variant Exon 31 of 33 1 NM_015028.4 ENSP00000399511.2 Q9UKE5-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151812
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461686
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727124
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151812
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74114
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3826G>A (p.V1276M) alteration is located in exon 31 (coding exon 31) of the TNIK gene. This alteration results from a G to A substitution at nucleotide position 3826, causing the valine (V) at amino acid position 1276 to be replaced by a methionine (M). 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
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;.;.;.;.;.;.;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D;D
M_CAP
Benign
0.0091
T
MetaRNN
Uncertain
0.65
D;D;D;D;D;D;D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.1
M;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-2.6
D;D;D;D;D;D;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.021
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.030
D;D;D;D;D;D;D;D
Polyphen
0.99
D;D;D;D;P;D;D;P
Vest4
0.69
MutPred
0.69
Gain of glycosylation at T1272 (P = 0.0185);.;.;.;.;.;.;.;
MVP
0.29
MPC
2.3
ClinPred
0.97
D
GERP RS
5.9
Varity_R
0.35
gMVP
0.62

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: rs1408774884; hg19: chr3-170784398; API