17-39829548-A-C

Variant names:

• chr17-39829548-A-C
• rs3816470
• NM_012481.5:c.62-60T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012481.5(IKZF3):​c.62-60T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IKZF3 NM_012481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• Publications: 47 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 84

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012481.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	NM_012481.5	MANE Select	c.62-60T>G		intron	N/A	NP_036613.2
	IKZF3	NM_001257408.2		c.61+2550T>G		intron	N/A	NP_001244337.1	Q9UKT9-7
	IKZF3	NM_183229.3		c.62-60T>G		intron	N/A	NP_899052.1	Q9UKT9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF3	ENST00000346872.8	TSL:1 MANE Select	c.62-60T>G		intron	N/A	ENSP00000344544.3	Q9UKT9-1
	IKZF3	ENST00000535189.5	TSL:1	c.61+2550T>G		intron	N/A	ENSP00000438972.1	Q9UKT9-7
	IKZF3	ENST00000439167.6	TSL:1	c.61+2550T>G		intron	N/A	ENSP00000403776.2	Q9UKT9-8

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4734

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.85

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

Other links and lift over

dbSNP: rs3816470; hg19: chr17-37985801;