Genetic Variant NM_025194.3:c.1156-3277G>T (chr19-40722063-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.259

Publications

21 publications found

Variant links:

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]

ITPKC links:

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

COQ8B links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPKC	NM_025194.3 link	c.1156-3277G>T		intron_variant	Intron 1 of 6	ENST00000263370.3	NP_079470.1	Q96DU7A0A024R0N8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPKC	ENST00000263370.3 link	c.1156-3277G>T		intron_variant	Intron 1 of 6	1	NM_025194.3	ENSP00000263370.1		Q96DU7

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52423

AN:

151440

Hom.:

9374

Cov.:

show subpopulations

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.:

AF XY:

0.350

AC XY:

25873

AN XY:

74022

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1691

3382

5074

6765

8456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over