Genetic Variant NM_025194.3:c.*913G>C (chr19-40740473-G-C) – 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.*913G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 203,946 control chromosomes in the GnomAD database, including 23,132 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 0.46 ( 16846 hom., cov: 33)

Exomes 𝑓: 0.48 ( 6286 hom. )

Consequence

ITPKC
NM_025194.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.95

Publications

22 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:

Genome browser will be placed here

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 (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ITPKC	NM_025194.3 link	c.*913G>C	3_prime_UTR_variant	Exon 7 of 7	ENST00000263370.3	NP_079470.1	Q96DU7A0A024R0N8
ITPKC	NM_001411098.1 link	c.*913G>C	3_prime_UTR_variant	Exon 6 of 6		NP_001398027.1
ITPKC	XM_047439466.1 link	c.*543G>C	3_prime_UTR_variant	Exon 8 of 8		XP_047295422.1
ITPKC	XM_047439468.1 link	c.*1622G>C	3_prime_UTR_variant	Exon 7 of 7		XP_047295424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPKC	ENST00000263370.3 link	c.*913G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_025194.3	ENSP00000263370.1		Q96DU7

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69682

AN:

151994

Hom.:

16829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.475

GnomAD4 exome

AF:

0.484

AC:

25107

AN:

51834

Hom.:

6286

Cov.:

AF XY:

0.486

AC XY:

13090

AN XY:

26924

show subpopulations

African (AFR)

AF:

0.253

AC:

377

AN:

1488

American (AMR)

AF:

0.621

AC:

749

AN:

1206

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

681

AN:

1778

East Asian (EAS)

AF:

0.582

AC:

2635

AN:

4524

South Asian (SAS)

AF:

0.579

AC:

270

AN:

466

European-Finnish (FIN)

AF:

0.514

AC:

3055

AN:

5942

Middle Eastern (MID)

AF:

0.430

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.478

AC:

15820

AN:

33100

Other (OTH)

AF:

0.458

AC:

1421

AN:

3100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

593

1186

1778

2371

2964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.458

AC:

69721

AN:

152112

Hom.:

16846

Cov.:

AF XY:

0.463

AC XY:

34470

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.309

AC:

12812

AN:

41522

American (AMR)

AF:

0.564

AC:

8623

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1481

AN:

3472

East Asian (EAS)

AF:

0.546

AC:

2815

AN:

5158

South Asian (SAS)

AF:

0.582

AC:

2808

AN:

4822

European-Finnish (FIN)

AF:

0.539

AC:

5698

AN:

10574

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.498

AC:

33836

AN:

67970

Other (OTH)

AF:

0.477

AC:

1006

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1935

3870

5804

7739

9674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<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:

0.337

Hom.:

960

Bravo

AF:

0.453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.017

(source)

DANN

Benign

0.37

PhyloP100

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over