Genetic Variant CBFA2T3:p.Val482Leu (chr16-88880747-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005187.6(CBFA2T3):c.1444G>T(p.Val482Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CBFA2T3
NM_005187.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Publications

0 publications found

Variant links:

Genes affected

CBFA2T3 (HGNC:1537): (CBFA2/RUNX1 partner transcriptional co-repressor 3) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(16;21)(q24;q22) translocation is one of the less common karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. This gene is also a putative breast tumor suppressor. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

CBFA2T3 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.16272888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBFA2T3	NM_005187.6 link	c.1444G>T	p.Val482Leu	missense_variant	Exon 10 of 12	ENST00000268679.9	NP_005178.4	O75081-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBFA2T3	ENST00000268679.9 link	c.1444G>T	p.Val482Leu	missense_variant	Exon 10 of 12	1	NM_005187.6	ENSP00000268679.4		O75081-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1425424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705742

African (AFR)

AF:

0.00

AC:

AN:

32718

American (AMR)

AF:

0.00

AC:

AN:

40672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25498

East Asian (EAS)

AF:

0.00

AC:

AN:

37774

South Asian (SAS)

AF:

0.00

AC:

AN:

81496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093244

Other (OTH)

AF:

0.00

AC:

AN:

58958

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1444G>T (p.V482L) alteration is located in exon 10 (coding exon 10) of the CBFA2T3 gene. This alteration results from a G to T substitution at nucleotide position 1444, causing the valine (V) at amino acid position 482 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N

PhyloP100

1.4

PrimateAI

Benign

0.46

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.082

Sift

Benign

0.093

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0020

B;B

Vest4

0.23

MutPred

0.31

.;Loss of MoRF binding (P = 0.1692);

MVP

0.28

MPC

0.71

ClinPred

0.25

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over