rs2088885

Variant names:

• chr3-171253502-C-A
• rs2088885
• NM_015028.4:c.124-25281G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-171253502-C-A
• chr3-171253502-C-T

Variant summary

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

The NM_015028.4(TNIK):​c.124-25281G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 150,380 control chromosomes in the GnomAD database, including 23,716 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 (23716 hom., cov: 26)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIK	NM_015028.4	c.124-25281G>T		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.124-25281G>T		intron_variant	Intron 2 of 32	1	NM_015028.4	ENSP00000399511.2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83163 AN: 150264 Hom.: 23687 Cov.: 26

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.554 AC: 83259 AN: 150380 Hom.: 23716 Cov.: 26 AF XY: 0.550 AC XY: 40330 AN XY: 73274

African (AFR) AF: 0.672 AC: 27500 AN: 40904

American (AMR) AF: 0.461 AC: 6976 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3466

East Asian (EAS) AF: 0.340 AC: 1736 AN: 5110

South Asian (SAS) AF: 0.432 AC: 2050 AN: 4742

European-Finnish (FIN) AF: 0.594 AC: 5971 AN: 10054

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35463 AN: 67702

Other (OTH) AF: 0.525 AC: 1089 AN: 2074

Alfa AF: 0.533 Hom.: 12340

Bravo AF: 0.551

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2088885; hg19: chr3-170971291;