10-122993890-C-T

Variant names:

• chr10-122993890-C-T
• NM_001372123.1:c.1150G>A

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_001372123.1(IKZF5):​c.1150G>A​(p.Gly384Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IKZF5 NM_001372123.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.73
• Publications: 0 publications found

Genes affected

IKZF5 (HGNC:14283): (IKAROS family zinc finger 5) Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Pegasus, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]

PSTK (HGNC:28578): (phosphoseryl-tRNA kinase) Predicted to enable kinase activity and tRNA binding activity. Predicted to be involved in phosphorylation; selenocysteinyl-tRNA(Sec) biosynthetic process; and translation. Predicted to act upstream of or within selenocysteine incorporation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 5 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 1.8899 (below the threshold of 3.09). Trascript score misZ: 3.2196 (above the threshold of 3.09). GenCC associations: The gene is linked to thrombocytopenia 7, autosomal thrombocytopenia with normal platelets.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372123.1. 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
	IKZF5	NM_001372123.1	MANE Select	c.1150G>A	p.Gly384Arg	missense	Exon 5 of 5	NP_001359052.1	Q9H5V7
	IKZF5	NM_001271840.1		c.1150G>A	p.Gly384Arg	missense	Exon 5 of 5	NP_001258769.1	Q9H5V7
	IKZF5	NM_001372125.1		c.1150G>A	p.Gly384Arg	missense	Exon 5 of 5	NP_001359054.1	Q9H5V7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKZF5	ENST00000368886.10	TSL:1 MANE Select	c.1150G>A	p.Gly384Arg	missense	Exon 5 of 5	ENSP00000357881.5	Q9H5V7
	IKZF5	ENST00000617859.4	TSL:1	c.1150G>A	p.Gly384Arg	missense	Exon 5 of 5	ENSP00000478056.1	Q9H5V7
	IKZF5	ENST00000904853.1		c.1174G>A	p.Gly392Arg	missense	Exon 5 of 5	ENSP00000574912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.25	N
PhyloP100		7.7
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.44	T
Polyphen		1.0	D
Vest4		0.78
MutPred		0.73		Gain of solvent accessibility (P = 0.0584)
MVP		0.43
MPC		1.7
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.86
gMVP		0.63
Mutation Taster		=19/81	disease causing

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

hg19: chr10-124753406;