3-171421678-A-G

Variant names:

• chr3-171421678-A-G
• rs7650598
• NM_015028.4:c.57+38329T>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+38329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 150,234 control chromosomes in the GnomAD database, including 44,988 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 0.77 (44988 hom., cov: 27)
• Consequence: TNIK NM_015028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIK	NM_015028.4	c.57+38329T>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+38329T>C		intron_variant	Intron 1 of 32	1	NM_015028.4	ENSP00000399511.2

Frequencies

GnomAD3 genomes AF: 0.773 AC: 115977 AN: 150122 Hom.: 44941 Cov.: 27

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.773 AC: 116077 AN: 150234 Hom.: 44988 Cov.: 27 AF XY: 0.772 AC XY: 56479 AN XY: 73156

African (AFR) AF: 0.841 AC: 34163 AN: 40608

American (AMR) AF: 0.751 AC: 11269 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2660 AN: 3468

East Asian (EAS) AF: 0.681 AC: 3477 AN: 5104

South Asian (SAS) AF: 0.671 AC: 3205 AN: 4774

European-Finnish (FIN) AF: 0.758 AC: 7652 AN: 10094

Middle Eastern (MID) AF: 0.866 AC: 253 AN: 292

European-Non Finnish (NFE) AF: 0.753 AC: 51106 AN: 67884

Other (OTH) AF: 0.783 AC: 1641 AN: 2096

Alfa AF: 0.762 Hom.: 83637

Bravo AF: 0.777

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.36
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: rs7650598; hg19: chr3-171139467;