Variant 17-39766242-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012481.5(IKZF3):c.1078G>A(p.Glu360Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000604 in 1,613,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

IKZF3
NM_012481.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

IKZF3 (HGNC:13178): (IKAROS family zinc finger 3) This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this protein family (Ikaros, Aiolos and Helios) are hematopoietic-specific transcription factors involved in the regulation of lymphocyte development. This gene product is a transcription factor that is important in the regulation of B lymphocyte proliferation and differentiation. Both Ikaros and Aiolos can participate in chromatin remodeling. Regulation of gene expression in B lymphocytes by Aiolos is complex as it appears to require the sequential formation of Ikaros homodimers, Ikaros/Aiolos heterodimers, and Aiolos homodimers. Several alternative transcripts encoding different isoforms have been described, as well as some non-protein coding variants. [provided by RefSeq, Apr 2012]

IKZF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07280803).

BS2

High AC in GnomAd4 at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKZF3	NM_012481.5 linkuse as main transcript	c.1078G>A	p.Glu360Lys	missense_variant	8/8	ENST00000346872.8	NP_036613.2	Q9UKT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8 linkuse as main transcript	c.1078G>A	p.Glu360Lys	missense_variant	8/8	1	NM_012481.5	ENSP00000344544.3		Q9UKT9-1

Frequencies

GnomAD3 genomes

AF:

0.000671

AC:

102

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000402

AC:

101

AN:

251404

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000597

AC:

873

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000582

AC XY:

423

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000706

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000671

AC:

102

AN:

152094

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000665

Hom.:

Bravo

AF:

0.000676

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

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

Aug 02, 2021

The c.1078G>A (p.E360K) alteration is located in exon 8 (coding exon 8) of the IKZF3 gene. This alteration results from a G to A substitution at nucleotide position 1078, causing the glutamic acid (E) at amino acid position 360 to be replaced by a lysine (K). 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

0.24

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D;D;D;.;D;D;D;D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.073

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.7

M;.;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.95

D;D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

.;.;.;N;N;N;N;N;N;.;N;N;N;N;.

REVEL

Benign

0.11

Sift

Benign

0.32

.;.;.;T;T;T;T;T;T;.;T;T;T;T;.

Sift4G

Benign

0.90

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.33

B;.;P;P;P;P;P;B;P;.;P;P;B;B;P

Vest4

0.43

MVP

0.44

MPC

0.88

ClinPred

0.054

GERP RS

5.7

Varity_R

0.17

gMVP

0.45

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

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