rs9814699

Positions:

• chr3-171159321-G-A
• chr3-171159321-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105374216 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIK	NM_015028.4	c.1017-1657C>T		intron_variant		ENST00000436636.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIK	ENST00000436636.7	c.1017-1657C>T		intron_variant		1	NM_015028.4	A1

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

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.562

Alfa AF: 0.480 Hom.: 2303

Bravo AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs9814699; hg19: chr3-170877110;