10-122996010-GTGTT-AATCCACA

Position:

• chr10-122996010-GTGTT-AATCCACA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4_Supporting PP3 PP5_Moderate

The NM_001372123.1(IKZF5):​c.296_300delinsTGTGGATT​(p.Glu99_His100delinsValTrpIle) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IKZF5 NM_001372123.1 protein_altering
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.52

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001372123.1. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 10-122996010-GTGTT-AATCCACA is Pathogenic according to our data. Variant chr10-122996010-GTGTT-AATCCACA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2671954.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKZF5	NM_001372123.1	c.296_300delinsTGTGGATT	p.Glu99_His100delinsValTrpIle	protein_altering_variant	4/5	ENST00000368886.10	NP_001359052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKZF5	ENST00000368886.10	c.296_300delinsTGTGGATT	p.Glu99_His100delinsValTrpIle	protein_altering_variant	4/5	1	NM_001372123.1	ENSP00000357881	P1
IKZF5	ENST00000617859.4	c.296_300delinsTGTGGATT	p.Glu99_His100delinsValTrpIle	protein_altering_variant	4/5	1		ENSP00000478056	P1
IKZF5	ENST00000496605.5	n.594_598delinsTGTGGATT		non_coding_transcript_exon_variant	4/4	2
PSTK	ENST00000497219.5	n.1816-1109_1816-1105delinsAATCCACA		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thrombocytopenia 7 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Nov 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr10-124755526;