Genetic Variant TNIK:c.3449-7A>T (chr3-171071330-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_015028.4(TNIK):c.3449-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,555,952 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 49 hom. )

Consequence

TNIK
NM_015028.4 splice_region, intron

Scores

Splicing: ADA: 0.0002403

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.728

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]

TNIK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 3-171071330-T-A is Benign according to our data. Variant chr3-171071330-T-A is described in ClinVar as [Benign]. Clinvar id is 769283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIK	NM_015028.4 link	c.3449-7A>T		splice_region_variant, intron_variant	Intron 28 of 32	ENST00000436636.7	NP_055843.1	Q9UKE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7 link	c.3449-7A>T		splice_region_variant, intron_variant	Intron 28 of 32	1	NM_015028.4	ENSP00000399511.2		Q9UKE5-1

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

622

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00565

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00507

AC:

932

AN:

183662

Hom.:

AF XY:

0.00577

AC XY:

566

AN XY:

98126

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.00113

Gnomad EAS exome

AF:

0.0000715

Gnomad SAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.000552

Gnomad NFE exome

AF:

0.00600

Gnomad OTH exome

AF:

0.00702

GnomAD4 exome

AF:

0.00604

AC:

8484

AN:

1403658

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4398

AN XY:

695204

show subpopulations

Gnomad4 AFR exome

AF:

0.000899

Gnomad4 AMR exome

AF:

0.00395

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.0000520

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.000664

Gnomad4 NFE exome

AF:

0.00622

Gnomad4 OTH exome

AF:

0.00647

GnomAD4 genome

AF:

0.00408

AC:

621

AN:

152294

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00565

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00484

Hom.:

Bravo

AF:

0.00479

Asia WGS

AF:

0.00434

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TNIK: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.44

CADD

Benign

6.2

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.0060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over