NM_015028.4:c.124-6313G>A

Variant names:

• chr3-171234534-C-T
• rs905129
• NM_015028.4:c.124-6313G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015028.4(TNIK):​c.124-6313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,936 control chromosomes in the GnomAD database, including 24,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24528 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 54

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIK	NM_015028.4	c.124-6313G>A		intron_variant	Intron 2 of 32	ENST00000436636.7	NP_055843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7	c.124-6313G>A		intron_variant	Intron 2 of 32	1	NM_015028.4	ENSP00000399511.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83617 AN: 151818 Hom.: 24483 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.551 AC: 83716 AN: 151936 Hom.: 24528 Cov.: 32 AF XY: 0.544 AC XY: 40416 AN XY: 74234

African (AFR) AF: 0.762 AC: 31560 AN: 41442

American (AMR) AF: 0.484 AC: 7394 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1881 AN: 3466

East Asian (EAS) AF: 0.353 AC: 1822 AN: 5162

South Asian (SAS) AF: 0.538 AC: 2583 AN: 4800

European-Finnish (FIN) AF: 0.418 AC: 4397 AN: 10512

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32361 AN: 67962

Other (OTH) AF: 0.578 AC: 1217 AN: 2106

Alfa AF: 0.503 Hom.: 11078

Bravo AF: 0.562

Asia WGS AF: 0.484 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.32
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs905129; hg19: chr3-170952323;