Variant 3-108568239-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020890.3(CIP2A):c.1189C>T(p.Leu397Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CIP2A
NM_020890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

CIP2A (HGNC:29302): (cellular inhibitor of PP2A) Enables protein homodimerization activity. Predicted to act upstream of or within positive regulation of neural precursor cell proliferation and spermatogenesis. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CIP2A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CIP2A	NM_020890.3 linkuse as main transcript	c.1189C>T	p.Leu397Phe	missense_variant	10/21	ENST00000295746.13	NP_065941.2
CIP2A	XM_006713716.4 linkuse as main transcript	c.1186C>T	p.Leu396Phe	missense_variant	10/21		XP_006713779.1
CIP2A	XM_011513057.3 linkuse as main transcript	c.247C>T	p.Leu83Phe	missense_variant	3/14		XP_011511359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIP2A	ENST00000295746.13 linkuse as main transcript	c.1189C>T	p.Leu397Phe	missense_variant	10/21	1	NM_020890.3	ENSP00000295746	P1	Q8TCG1-1
CIP2A	ENST00000491772.5 linkuse as main transcript	c.712C>T	p.Leu238Phe	missense_variant	10/21	1		ENSP00000419487		Q8TCG1-2
CIP2A	ENST00000487834.5 linkuse as main transcript	n.1458C>T		non_coding_transcript_exon_variant	10/14	1
CIP2A	ENST00000481530.5 linkuse as main transcript	c.*759C>T		3_prime_UTR_variant, NMD_transcript_variant	10/21	1		ENSP00000417297

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.1189C>T (p.L397F) alteration is located in exon 10 (coding exon 10) of the KIAA1524 gene. This alteration results from a C to T substitution at nucleotide position 1189, causing the leucine (L) at amino acid position 397 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.082

T;.;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D;.

REVEL

Benign

0.25

Sift

Uncertain

0.014

D;D;.

Sift4G

Uncertain

0.048

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.68

MVP

0.72

MPC

0.67

ClinPred

0.96

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.66

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over