1-74268759-C-T

Position:

• chr1-74268759-C-T

Variant summary

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

The NM_015978.3(TNNI3K):​c.334-2839C>T 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 151,794 control chromosomes in the GnomAD database, including 1,299 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 (1299 hom., cov: 32)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNI3K	NM_015978.3	c.334-2839C>T		intron_variant		ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3	c.637-2839C>T		intron_variant			NP_001106279.3
FPGT-TNNI3K	NM_001199327.2	c.637-2839C>T		intron_variant			NP_001186256.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNI3K	ENST00000326637.8	c.334-2839C>T		intron_variant		1	NM_015978.3	ENSP00000322251.3
FPGT-TNNI3K	ENST00000557284.7	c.637-2839C>T		intron_variant		2		ENSP00000450895.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16968 AN: 151676 Hom.: 1296 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.112 AC: 16991 AN: 151794 Hom.: 1299 Cov.: 32 AF XY: 0.110 AC XY: 8146 AN XY: 74208

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0903

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0626

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.0707 Hom.: 623

Bravo AF: 0.120

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.74

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: rs10493540; hg19: chr1-74734443; COSMIC: COSV58549092;