ENST00000293068.9:n.-40A>T

Variant names:

• chr17-39864228-G-A
• NM_012481.5:c.-102C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000293068.9(IKZF3):​n.-102C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,220,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: IKZF3 ENST00000293068.9 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 0 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKZF3	NM_012481.5	c.-102C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000346872.8	NP_036613.2
IKZF3	NM_012481.5	c.-102C>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000346872.8	NP_036613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKZF3	ENST00000346872.8	c.-102C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1	NM_012481.5	ENSP00000344544.3
IKZF3	ENST00000346872.8	c.-102C>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_012481.5	ENSP00000344544.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000328 AC: 4 AN: 1220306 Hom.: 0 Cov.: 16 AF XY: 0.00000328 AC XY: 2 AN XY: 610372

African (AFR) AF: 0.00 AC: 0 AN: 24364

American (AMR) AF: 0.00 AC: 0 AN: 29936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20156

East Asian (EAS) AF: 0.00 AC: 0 AN: 34214

South Asian (SAS) AF: 0.00 AC: 0 AN: 71462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3850

European-Non Finnish (NFE) AF: 0.00000428 AC: 4 AN: 935480

Other (OTH) AF: 0.00 AC: 0 AN: 51142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		0.077
PromoterAI		0.0020	Neutral

Splicing

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

Other links and lift over

hg19: chr17-38020481;