chr1-74235485-TGTACTG-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_015978.3(TNNI3K):​c.38_40+3del variant causes a inframe deletion, splice region change. The variant allele was found at a frequency of 0.00000152 in 1,312,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

TNNI3K
NM_015978.3 inframe_deletion, splice_region

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_015978.3.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNNI3KNM_015978.3 linkuse as main transcriptc.38_40+3del inframe_deletion, splice_region_variant 1/25 ENST00000326637.8
FPGT-TNNI3KNM_001112808.3 linkuse as main transcriptc.344-613_344-608del intron_variant
FPGT-TNNI3KNM_001199327.2 linkuse as main transcriptc.344-613_344-608del intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNNI3KENST00000326637.8 linkuse as main transcriptc.38_40+3del inframe_deletion, splice_region_variant 1/251 NM_015978.3 P1Q59H18-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000451
AC:
1
AN:
221658
Hom.:
0
AF XY:
0.00000826
AC XY:
1
AN XY:
121022
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000944
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000152
AC:
2
AN:
1312220
Hom.:
0
AF XY:
0.00000303
AC XY:
2
AN XY:
659570
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000101
Gnomad4 OTH exome
AF:
0.0000182
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeOct 13, 2023This variant, c.38_40+3del, is a complex sequence change that results in the deletion of 3 and insertion of 1 amino acid(s) in the TNNI3K protein (Splice site). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with TNNI3K-related conditions. This variant is also known as c.38_40+3del. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1211423908; hg19: chr1-74701169; API