Variant 10-122994678-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate

The NM_001372123.1(IKZF5):c.362A>T(p.Tyr121Phe) variant causes a missense 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 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 8.02

Variant links:

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]

IKZF5 links:

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]

PSTK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), IKZF5. . Gene score misZ 1.8899 (greater than the threshold 3.09). Trascript score misZ 3.2196 (greater than threshold 3.09). GenCC has associacion of gene with thrombocytopenia 7, autosomal thrombocytopenia with normal platelets.

PP5

Variant 10-122994678-T-A is Pathogenic according to our data. Variant chr10-122994678-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1703863.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 linkuse as main transcript	c.362A>T	p.Tyr121Phe	missense_variant	5/5	ENST00000368886.10	NP_001359052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IKZF5	ENST00000368886.10 linkuse as main transcript	c.362A>T	p.Tyr121Phe	missense_variant	5/5	1	NM_001372123.1	ENSP00000357881	P1
IKZF5	ENST00000617859.4 linkuse as main transcript	c.362A>T	p.Tyr121Phe	missense_variant	5/5	1		ENSP00000478056	P1
PSTK	ENST00000496079.1 linkuse as main transcript	n.621T>A		non_coding_transcript_exon_variant	5/5	3
PSTK	ENST00000497219.5 linkuse as main transcript	n.1816-2441T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Thrombocytopenia 7

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology

Jun 30, 2023

Functional data show impaired DNA binding -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;.

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.9

N;.

REVEL

Uncertain

0.30

Sift

Benign

0.092

T;.

Sift4G

Benign

0.19

T;T

Polyphen

1.0

D;D

Vest4

0.59

MutPred

0.29

Loss of phosphorylation at Y121 (P = 0.1059);Loss of phosphorylation at Y121 (P = 0.1059);

MVP

0.64

MPC

1.5

ClinPred

0.85

GERP RS

6.0

Varity_R

0.22

gMVP

0.56

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over