Menu
GeneBe

17-39765833-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_012481.5(IKZF3):c.1487C>G(p.Ser496Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

IKZF3
NM_012481.5 missense

Scores

7
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IKZF3NM_012481.5 linkuse as main transcriptc.1487C>G p.Ser496Trp missense_variant 8/8 ENST00000346872.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IKZF3ENST00000346872.8 linkuse as main transcriptc.1487C>G p.Ser496Trp missense_variant 8/81 NM_012481.5 P1Q9UKT9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAiLife Diagnostics, AiLife DiagnosticsAug 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
Cadd
Pathogenic
33
Dann
Uncertain
0.99
Eigen
Pathogenic
0.97
Eigen_PC
Pathogenic
0.92
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D;D;D;.;D;D;D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.77
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.6
M;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
REVEL
Uncertain
0.59
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;D;D;D;D;D;D;D;.;D;D;D;D;D
Vest4
0.65
MutPred
0.63
Loss of disorder (P = 0);.;.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP
0.49
MPC
1.9
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.87
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-37922086; API