rs9810370

Positions:

• chr3-171149911-T-A
• chr3-171149911-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015028.4(TNIK):​c.1221+7549A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,096 control chromosomes in the GnomAD database, including 23,524 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 0.53 (23524 hom., cov: 32)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIK	NM_015028.4	c.1221+7549A>T		intron_variant		ENST00000436636.7	NP_055843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIK	ENST00000436636.7	c.1221+7549A>T		intron_variant		1	NM_015028.4	ENSP00000399511.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80310 AN: 151976 Hom.: 23527 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.528 AC: 80314 AN: 152096 Hom.: 23524 Cov.: 32 AF XY: 0.533 AC XY: 39623 AN XY: 74358

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.509

Alfa AF: 0.573 Hom.: 3316

Bravo AF: 0.511

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9810370; hg19: chr3-170867700;