19-40720510-C-G

Variant names:

• chr19-40720510-C-G
• rs2561528
• NM_025194.3:c.1155+2220C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025194.3(ITPKC):​c.1155+2220C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,708 control chromosomes in the GnomAD database, including 32,913 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 0.65 (32913 hom., cov: 29)
• Consequence: ITPKC NM_025194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 8 publications found

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]

COQ8B Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• nephrotic syndrome, type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025194.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	NM_025194.3	MANE Select	c.1155+2220C>G		intron	N/A	NP_079470.1
	ITPKC	NM_001411098.1		c.1155+2220C>G		intron	N/A	NP_001398027.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	ENST00000263370.3	TSL:1 MANE Select	c.1155+2220C>G		intron	N/A	ENSP00000263370.1
	ITPKC	ENST00000699490.1		c.1155+2220C>G		intron	N/A	ENSP00000514401.1
	ITPKC	ENST00000699489.1		c.1155+2220C>G		intron	N/A	ENSP00000514400.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99005 AN: 151590 Hom.: 32867 Cov.: 29

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.653 AC: 99107 AN: 151708 Hom.: 32913 Cov.: 29 AF XY: 0.655 AC XY: 48525 AN XY: 74106

African (AFR) AF: 0.756 AC: 31281 AN: 41358

American (AMR) AF: 0.685 AC: 10430 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3706 AN: 5146

South Asian (SAS) AF: 0.642 AC: 3093 AN: 4816

European-Finnish (FIN) AF: 0.635 AC: 6676 AN: 10510

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40013 AN: 67884

Other (OTH) AF: 0.626 AC: 1319 AN: 2106

Alfa AF: 0.621 Hom.: 3471

Bravo AF: 0.661

Asia WGS AF: 0.694 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.30
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs2561528; hg19: chr19-41226415;