1-74235611-T-C

Variant names:

• chr1-74235611-T-C
• rs505508
• NM_015978.3:c.40+120T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015978.3(TNNI3K):​c.40+120T>C 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: 31)
• Consequence: TNNI3K NM_015978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNI3K	NM_015978.3	c.40+120T>C		intron_variant	Intron 1 of 24	ENST00000326637.8	NP_057062.1
FPGT-TNNI3K	NM_001112808.3	c.344-491T>C		intron_variant	Intron 3 of 26		NP_001106279.3
FPGT-TNNI3K	NM_001199327.2	c.344-491T>C		intron_variant	Intron 3 of 23		NP_001186256.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNI3K	ENST00000326637.8	c.40+120T>C		intron_variant	Intron 1 of 24	1	NM_015978.3	ENSP00000322251.3
FPGT-TNNI3K	ENST00000557284.7	c.344-491T>C		intron_variant	Intron 3 of 26	2		ENSP00000450895.3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-1.0
PromoterAI		-0.0070	Neutral

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: rs505508; hg19: chr1-74701295;