19-40717326-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_025194.3(ITPKC):c.191G>A(p.Gly64Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,595,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

ITPKC
NM_025194.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.635

Publications

1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COQ8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033649117).

BP6

Variant 19-40717326-G-A is Benign according to our data. Variant chr19-40717326-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3530841.Status of the report is criteria_provided_single_submitter, 1 stars.

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.191G>A	p.Gly64Glu	missense	Exon 1 of 7	NP_079470.1	Q96DU7
	ITPKC	NM_001411098.1		c.191G>A	p.Gly64Glu	missense	Exon 1 of 6	NP_001398027.1	A0A8V8TPP3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPKC	ENST00000263370.3	TSL:1 MANE Select	c.191G>A	p.Gly64Glu	missense	Exon 1 of 7	ENSP00000263370.1	Q96DU7
ITPKC	ENST00000699490.1		c.191G>A	p.Gly64Glu	missense	Exon 1 of 8	ENSP00000514401.1	Q96DU7
ITPKC	ENST00000699489.1		c.191G>A	p.Gly64Glu	missense	Exon 1 of 6	ENSP00000514400.1	A0A8V8TPP3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000857

AC:

AN:

210006

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.0000883

Gnomad AMR exome

AF:

0.000127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

235

AN:

1443724

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

109

AN XY:

717240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.0000942

AC:

AN:

42442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25806

East Asian (EAS)

AF:

0.00

AC:

AN:

39082

South Asian (SAS)

AF:

0.00

AC:

AN:

84868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47932

Middle Eastern (MID)

AF:

0.000195

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

0.000205

AC:

227

AN:

1105550

Other (OTH)

AF:

0.0000503

AC:

AN:

59692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.000197

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

67902

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000260

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000422

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.3

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.24

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.46

M_CAP

Benign

0.0031

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

PhyloP100

-0.64

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.21

REVEL

Benign

0.020

Sift

Benign

0.79

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.075

MVP

0.25

MPC

0.47

ClinPred

0.020

GERP RS

-5.8

PromoterAI

0.13

Neutral

(source)

Varity_R

0.038

gMVP

0.068

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over