19-40717264-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_025194.3(ITPKC):c.129G>T(p.Gly43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,397,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000060 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
ITPKC
NM_025194.3 synonymous
NM_025194.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00600
Genes affected
ITPKC (HGNC:14897): (inositol-trisphosphate 3-kinase C) This gene encodes a member of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase family of enzymes that catalyze the phosphorylation of inositol 1,4,5-trisphosphate to 1,3,4,5-tetrakisphosphate. The encoded protein is localized to the nucleus and cytoplasm and has both nuclear import and nuclear export activity. Single nucleotide polymorphisms in this gene are associated with Kawasaki disease.[provided by RefSeq, Sep 2009]
COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 19-40717264-G-T is Benign according to our data. Variant chr19-40717264-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045866.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.006 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPKC | NM_025194.3 | c.129G>T | p.Gly43= | synonymous_variant | 1/7 | ENST00000263370.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPKC | ENST00000263370.3 | c.129G>T | p.Gly43= | synonymous_variant | 1/7 | 1 | NM_025194.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000596 AC: 9AN: 150944Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.0000262 AC: 1AN: 38212Hom.: 0 AF XY: 0.0000500 AC XY: 1AN XY: 20012
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GnomAD4 exome AF: 0.0000329 AC: 41AN: 1246562Hom.: 0 Cov.: 30 AF XY: 0.0000428 AC XY: 26AN XY: 607334
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GnomAD4 genome ? AF: 0.0000596 AC: 9AN: 151052Hom.: 1 Cov.: 31 AF XY: 0.0000812 AC XY: 6AN XY: 73908
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ITPKC-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 16, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at