chr1-74527379-C-A

Variant names:

• chr1-74527379-C-A
• NM_015978.3:c.2352-12855C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015978.3(TNNI3K):​c.2352-12855C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNI3K	NM_015978.3	c.2352-12855C>A		intron_variant	Intron 23 of 24	ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3	c.2655-12855C>A		intron_variant	Intron 25 of 26		NP_001106279.3
LRRC53	XM_017003081.2	c.49+9425G>T		intron_variant	Intron 1 of 3		XP_016858570.1
LRRC53	XM_011542512.4	c.49+9425G>T		intron_variant	Intron 1 of 2		XP_011540814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNI3K	ENST00000326637.8	c.2352-12855C>A		intron_variant	Intron 23 of 24	1	NM_015978.3	ENSP00000322251.3
FPGT-TNNI3K	ENST00000557284.7	c.2655-12855C>A		intron_variant	Intron 25 of 26	2		ENSP00000450895.3
FPGT-TNNI3K	ENST00000648585.1	n.*2258-12855C>A		intron_variant	Intron 28 of 29			ENSP00000497631.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-74993063;