rs9814699

Variant names:

• chr3-171159321-G-A
• rs9814699
• NM_015028.4:c.1017-1657C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-171159321-G-A
• chr3-171159321-G-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.1017-1657C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,440 control chromosomes in the GnomAD database, including 23,329 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 (23329 hom., cov: 28)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 3 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):

• intellectual disability, autosomal recessive 54

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC105374216 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015028.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIK	NM_015028.4	MANE Select	c.1017-1657C>T		intron	N/A	NP_055843.1	Q9UKE5-1
	TNIK	NM_001161560.3		c.1017-1657C>T		intron	N/A	NP_001155032.1	Q9UKE5-4
	TNIK	NM_001161561.3		c.1017-1657C>T		intron	N/A	NP_001155033.1	Q9UKE5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIK	ENST00000436636.7	TSL:1 MANE Select	c.1017-1657C>T		intron	N/A	ENSP00000399511.2	Q9UKE5-1
	TNIK	ENST00000284483.12	TSL:1	c.1017-1657C>T		intron	N/A	ENSP00000284483.8	Q9UKE5-4
	TNIK	ENST00000357327.9	TSL:1	c.1017-1657C>T		intron	N/A	ENSP00000349880.5	Q9UKE5-2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82626 AN: 151322 Hom.: 23319 Cov.: 28

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.546 AC: 82676 AN: 151440 Hom.: 23329 Cov.: 28 AF XY: 0.552 AC XY: 40821 AN XY: 73944

African (AFR) AF: 0.425 AC: 17542 AN: 41282

American (AMR) AF: 0.606 AC: 9226 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2025 AN: 3464

East Asian (EAS) AF: 0.872 AC: 4445 AN: 5096

South Asian (SAS) AF: 0.622 AC: 2960 AN: 4762

European-Finnish (FIN) AF: 0.570 AC: 5942 AN: 10426

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38561 AN: 67870

Other (OTH) AF: 0.562 AC: 1183 AN: 2106

Alfa AF: 0.480 Hom.: 2303

Bravo AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.065
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: rs9814699; hg19: chr3-170877110;