Variant 3-171194514-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015028.4(TNIK):c.417+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,612,900 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 28 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 16 hom. )

Consequence

TNIK
NM_015028.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.597

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=-0.81).

BP6

Variant 3-171194514-T-G is Benign according to our data. Variant chr3-171194514-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 445516.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1535/152316) while in subpopulation AFR AF= 0.0353 (1466/41566). AF 95% confidence interval is 0.0338. There are 28 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIK	NM_015028.4 linkuse as main transcript	c.417+11A>C		intron_variant		ENST00000436636.7	NP_055843.1	Q9UKE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7 linkuse as main transcript	c.417+11A>C		intron_variant		1	NM_015028.4	ENSP00000399511.2		Q9UKE5-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1533

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00261

AC:

649

AN:

248516

Hom.:

AF XY:

0.00192

AC XY:

259

AN XY:

134828

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000948

AC:

1385

AN:

1460584

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

579

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.0339

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.0101

AC:

1535

AN:

152316

Hom.:

Cov.:

AF XY:

0.00953

AC XY:

710

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0353

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.0114

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Apr 19, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

DANN

Benign

0.55

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.

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