rs1333029

Positions:

• chr1-74283638-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNI3K	NM_015978.3	c.444+11930G>A		intron_variant		ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3	c.747+11930G>A		intron_variant			NP_001106279.3
FPGT-TNNI3K	NM_001199327.2	c.747+11930G>A		intron_variant			NP_001186256.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNI3K	ENST00000326637.8	c.444+11930G>A		intron_variant		1	NM_015978.3	ENSP00000322251.3
FPGT-TNNI3K	ENST00000557284.7	c.747+11930G>A		intron_variant		2		ENSP00000450895.3

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

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.0569

Gnomad4 NFE AF: 0.0695

Gnomad4 OTH AF: 0.0873

Alfa AF: 0.0971 Hom.: 202

Bravo AF: 0.120

Asia WGS AF: 0.0700 AC: 244 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.54

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: rs1333029; hg19: chr1-74749322;