rs10936688

chr3-171455766-G-Achr3-171455766-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.57+4241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,106 control chromosomes in the GnomAD database, including 41,783 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 0.73 (41783 hom., cov: 31)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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]

LOC124906303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIK	NM_015028.4	c.57+4241C>T		intron_variant		ENST00000436636.7
LOC124906303	XR_007096168.1	n.226+2180C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIK	ENST00000436636.7	c.57+4241C>T		intron_variant		1	NM_015028.4	A1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111363 AN: 151988 Hom.: 41739 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.733 AC: 111464 AN: 152106 Hom.: 41783 Cov.: 31 AF XY: 0.738 AC XY: 54845 AN XY: 74348

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.786

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.722

Alfa AF: 0.655 Hom.: 59626

Bravo AF: 0.736

Asia WGS AF: 0.756 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10936688; hg19: chr3-171173555;