12-56034844-G-C

Position:

• chr12-56034844-G-C

Variant summary

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

The NM_022465.4(IKZF4):​c.1271G>C​(p.Gly424Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IKZF4 NM_022465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.65

Genes affected

IKZF4 (HGNC:13179): (IKAROS family zinc finger 4) Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Eos, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]

(HGNC:):

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=0.182538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKZF4	NM_022465.4	c.1271G>C	p.Gly424Ala	missense_variant	8/8	ENST00000547167.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKZF4	ENST00000547167.6	c.1271G>C	p.Gly424Ala	missense_variant	8/8	1	NM_022465.4	P1
	ENST00000551846.1	n.183-5078C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1271G>C (p.G424A) alteration is located in exon 8 (coding exon 8) of the IKZF4 gene. This alteration results from a G to C substitution at nucleotide position 1271, causing the glycine (G) at amino acid position 424 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T;T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.88	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.42	N;.;N;N
REVEL	Benign	0.20
Sift	Benign	0.73	T;.;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.97	D;D;D;D
Vest4		0.26
MutPred		0.32		Loss of catalytic residue at G424 (P = 0.1009);Loss of catalytic residue at G424 (P = 0.1009);Loss of catalytic residue at G424 (P = 0.1009);.;
MVP		0.50
MPC		0.82
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.092
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-56428628;