NM_012481.5:c.1297A>C

Variant names:

• chr17-39766023-T-G
• NM_012481.5:c.1297A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012481.5(IKZF3):​c.1297A>C​(p.Ile433Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IKZF3 NM_012481.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06534308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.1297A>C	p.Ile433Leu	missense_variant	Exon 8 of 8	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.1297A>C	p.Ile433Leu	missense_variant	Exon 8 of 8	1	NM_012481.5	ENSP00000344544.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Benign	0.76
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.79	T;T;T;T;T;T;T;T;T;.;T;T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.065	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.40	.;.;.;N;N;N;N;N;N;.;N;N;N;N;.
REVEL	Benign	0.028
Sift	Benign	0.33	.;.;.;T;T;T;T;T;T;.;T;T;T;T;.
Sift4G	Benign	0.33	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;B;B;B;B;B;B;.;B;B;B;B;B
Vest4		0.14
MutPred		0.40		Gain of catalytic residue at I433 (P = 0.0064);.;.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP		0.29
MPC		0.60
ClinPred		0.064	T
GERP RS		-0.65
Varity_R		0.072
gMVP		0.081

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-37922276;