rs1514177

Positions:

• chr1-74525718-C-G

Variant summary

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

The NM_015978.3(TNNI3K):​c.2352-14516C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,968 control chromosomes in the GnomAD database, including 18,896 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 0.49 (18896 hom., cov: 32)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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]

LRRC53 (HGNC:25255): (leucine rich repeat containing 53) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNI3K	NM_015978.3	c.2352-14516C>G		intron_variant		ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3	c.2655-14516C>G		intron_variant			NP_001106279.3
LRRC53	XM_017003081.2	c.49+11086G>C		intron_variant			XP_016858570.1
LRRC53	XM_011542512.4	c.49+11086G>C		intron_variant			XP_011540814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNI3K	ENST00000326637.8	c.2352-14516C>G		intron_variant		1	NM_015978.3	ENSP00000322251.3
FPGT-TNNI3K	ENST00000557284.7	c.2655-14516C>G		intron_variant		2		ENSP00000450895.3
FPGT-TNNI3K	ENST00000648585.1	n.*2258-14516C>G		intron_variant				ENSP00000497631.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74180 AN: 151850 Hom.: 18887 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.488 AC: 74205 AN: 151968 Hom.: 18896 Cov.: 32 AF XY: 0.482 AC XY: 35779 AN XY: 74260

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.524

Alfa AF: 0.535 Hom.: 2770

Bravo AF: 0.475

Asia WGS AF: 0.400 AC: 1395 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	6.7
DANN	Benign	0.78

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: rs1514177; hg19: chr1-74991402;