rs1333029

Variant names:

• chr1-74283638-G-A
• rs1333029
• NM_015978.3:c.444+11930G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015978.3(TNNI3K):​c.444+11930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,100 control chromosomes in the GnomAD database, including 1,313 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 0.11 (1313 hom., cov: 32)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 4 publications found

Genes affected

TNNI3K (HGNC:19661): (TNNI3 interacting kinase) This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology. [provided by RefSeq, Sep 2012]

FPGT-TNNI3K (HGNC:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	NM_015978.3	MANE Select	c.444+11930G>A		intron	N/A	NP_057062.1	Q59H18-2
	FPGT-TNNI3K	NM_001112808.3		c.747+11930G>A		intron	N/A	NP_001106279.3
	FPGT-TNNI3K	NM_001199327.2		c.747+11930G>A		intron	N/A	NP_001186256.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI3K	ENST00000326637.8	TSL:1 MANE Select	c.444+11930G>A		intron	N/A	ENSP00000322251.3	Q59H18-2
	FPGT-TNNI3K	ENST00000557284.7	TSL:2	c.747+11930G>A		intron	N/A	ENSP00000450895.3
	FPGT-TNNI3K	ENST00000370899.7	TSL:2	c.747+11930G>A		intron	N/A	ENSP00000359936.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17073 AN: 151982 Hom.: 1310 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0882

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

GnomAD4 genome AF: 0.112 AC: 17096 AN: 152100 Hom.: 1313 Cov.: 32 AF XY: 0.110 AC XY: 8205 AN XY: 74376

African (AFR) AF: 0.217 AC: 9020 AN: 41482

American (AMR) AF: 0.0910 AC: 1390 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3470

East Asian (EAS) AF: 0.0624 AC: 323 AN: 5174

South Asian (SAS) AF: 0.0614 AC: 296 AN: 4820

European-Finnish (FIN) AF: 0.0569 AC: 602 AN: 10578

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0695 AC: 4722 AN: 67988

Other (OTH) AF: 0.0873 AC: 184 AN: 2108

Alfa AF: 0.100 Hom.: 224

Bravo AF: 0.120

Asia WGS AF: 0.0700 AC: 244 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.54
PhyloP100		0.81
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: rs1333029; hg19: chr1-74749322;