rs1501605

Variant names:

• chr3-171248627-A-G
• rs1501605
• NM_015028.4:c.124-20406T>C

Variant summary

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

The NM_015028.4(TNIK):​c.124-20406T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,148 control chromosomes in the GnomAD database, including 2,010 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 0.15 (2010 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIK	NM_015028.4	c.124-20406T>C		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.124-20406T>C		intron_variant	Intron 2 of 32	1	NM_015028.4	ENSP00000399511.2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22408 AN: 152030 Hom.: 2005 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.147 AC: 22415 AN: 152148 Hom.: 2010 Cov.: 32 AF XY: 0.153 AC XY: 11385 AN XY: 74382

African (AFR) AF: 0.0721 AC: 2993 AN: 41536

American (AMR) AF: 0.150 AC: 2287 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1834 AN: 5174

South Asian (SAS) AF: 0.222 AC: 1066 AN: 4808

European-Finnish (FIN) AF: 0.203 AC: 2151 AN: 10578

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11012 AN: 67984

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.157 Hom.: 4972

Bravo AF: 0.138

Asia WGS AF: 0.238 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.59
PhyloP100		-0.023
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: rs1501605; hg19: chr3-170966416;