3-171440696-C-G

Variant names:

• chr3-171440696-C-G
• rs2422299
• NM_015028.4:c.57+19311G>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.57+19311G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,118 control chromosomes in the GnomAD database, including 4,514 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 0.23 (4514 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• 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):

• 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 (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIK	NM_015028.4	c.57+19311G>C		intron_variant	Intron 1 of 32	ENST00000436636.7	NP_055843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7	c.57+19311G>C		intron_variant	Intron 1 of 32	1	NM_015028.4	ENSP00000399511.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34407 AN: 152000 Hom.: 4506 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.226 AC: 34438 AN: 152118 Hom.: 4514 Cov.: 32 AF XY: 0.226 AC XY: 16795 AN XY: 74388

African (AFR) AF: 0.282 AC: 11676 AN: 41474

American (AMR) AF: 0.271 AC: 4146 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.600 AC: 3104 AN: 5174

South Asian (SAS) AF: 0.175 AC: 842 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10586

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12003 AN: 67994

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.0767 Hom.: 98

Bravo AF: 0.246

Asia WGS AF: 0.356 AC: 1235 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	1.7
DANN	Benign	0.42
PhyloP100		0.19
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: rs2422299; hg19: chr3-171158485;