17-39766042-T-G

Variant names:

• chr17-39766042-T-G
• NM_012481.5:c.1278A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012481.5(IKZF3):​c.1278A>C​(p.Glu426Asp) 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: 0.265

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07744363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.1278A>C	p.Glu426Asp	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.1278A>C	p.Glu426Asp	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	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.93
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D;D;D;.;D;D;D;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.077	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.62	.;.;.;N;N;N;N;N;N;.;N;N;N;N;.
REVEL	Benign	0.028
Sift	Benign	0.53	.;.;.;T;T;T;T;T;T;.;T;T;T;T;.
Sift4G	Benign	0.73	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		0.068
MutPred		0.30		Gain of ubiquitination at K429 (P = 0.1306);.;.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP		0.24
MPC		0.55
ClinPred		0.18	T
GERP RS		0.94
Varity_R		0.11
gMVP		0.13

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: chr17-37922295;