chr3-171071247-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_015028.4(TNIK):​c.3525G>A​(p.Pro1175Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,603,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TNIK
NM_015028.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.998
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 3-171071247-C-T is Benign according to our data. Variant chr3-171071247-C-T is described in ClinVar as [Benign]. Clinvar id is 747587.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.998 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNIKNM_015028.4 linkc.3525G>A p.Pro1175Pro synonymous_variant Exon 29 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.3525G>A p.Pro1175Pro synonymous_variant Exon 29 of 33 1 NM_015028.4 ENSP00000399511.2 Q9UKE5-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152050
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000219
AC:
52
AN:
236954
Hom.:
0
AF XY:
0.000211
AC XY:
27
AN XY:
128064
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000304
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00252
Gnomad SAS exome
AF:
0.0000356
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000557
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000109
AC:
158
AN:
1451648
Hom.:
0
Cov.:
30
AF XY:
0.000105
AC XY:
76
AN XY:
721016
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000230
Gnomad4 ASJ exome
AF:
0.0000388
Gnomad4 EAS exome
AF:
0.00210
Gnomad4 SAS exome
AF:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000596
Gnomad4 OTH exome
AF:
0.000100
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.000132
Asia WGS
AF:
0.00116
AC:
4
AN:
3472

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TNIK-related disorder Benign:1
Aug 08, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
4.8
DANN
Benign
0.57

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: rs573971000; hg19: chr3-170789036; API