chr19-40722063-G-T

Variant names:

• chr19-40722063-G-T
• rs890934
• NM_025194.3:c.1156-3277G>T

Variant summary

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

The NM_025194.3(ITPKC):​c.1156-3277G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,558 control chromosomes in the GnomAD database, including 9,379 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 0.35 (9379 hom., cov: 30)
• Consequence: ITPKC NM_025194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 21 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 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.1156-3277G>T		intron	N/A	NP_079470.1	Q96DU7
	ITPKC	NM_001411098.1		c.1156-3277G>T		intron	N/A	NP_001398027.1	A0A8V8TPP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	ENST00000263370.3	TSL:1 MANE Select	c.1156-3277G>T		intron	N/A	ENSP00000263370.1	Q96DU7
	ITPKC	ENST00000699490.1		c.1156-3277G>T		intron	N/A	ENSP00000514401.1	Q96DU7
	ITPKC	ENST00000699489.1		c.1156-3277G>T		intron	N/A	ENSP00000514400.1	A0A8V8TPP3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52423 AN: 151440 Hom.: 9374 Cov.: 30

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.346 AC: 52445 AN: 151558 Hom.: 9379 Cov.: 30 AF XY: 0.350 AC XY: 25873 AN XY: 74022

African (AFR) AF: 0.271 AC: 11195 AN: 41296

American (AMR) AF: 0.409 AC: 6231 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2383 AN: 5126

South Asian (SAS) AF: 0.416 AC: 1992 AN: 4792

European-Finnish (FIN) AF: 0.385 AC: 4021 AN: 10448

Middle Eastern (MID) AF: 0.345 AC: 100 AN: 290

European-Non Finnish (NFE) AF: 0.358 AC: 24301 AN: 67896

Other (OTH) AF: 0.360 AC: 757 AN: 2102

Alfa AF: 0.354 Hom.: 15966

Bravo AF: 0.346

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs890934; hg19: chr19-41227968;