Variant chr16-88877209-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005187.6(CBFA2T3):c.1729G>A(p.Gly577Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,403,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CBFA2T3
NM_005187.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

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:

CBFA2T3 (HGNC:):

CBFA2T3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBFA2T3	NM_005187.6 linkuse as main transcript	c.1729G>A	p.Gly577Arg	missense_variant	12/12	ENST00000268679.9	NP_005178.4	O75081-1
CBFA2T3	NM_175931.3 linkuse as main transcript	c.1471G>A	p.Gly491Arg	missense_variant	11/11		NP_787127.1	O75081-2
CBFA2T3	XM_005256323.6 linkuse as main transcript	c.1654G>A	p.Gly552Arg	missense_variant	11/11		XP_005256380.1
CBFA2T3	XM_047434826.1 linkuse as main transcript	c.*1068G>A		3_prime_UTR_variant	11/11		XP_047290782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CBFA2T3	ENST00000268679.9 linkuse as main transcript	c.1729G>A	p.Gly577Arg	missense_variant	12/12	1	NM_005187.6	ENSP00000268679.4	O75081-1
CBFA2T3	ENST00000327483.9 linkuse as main transcript	c.1471G>A	p.Gly491Arg	missense_variant	11/11	1		ENSP00000332122.5	O75081-2
CBFA2T3	ENST00000563856.1 linkuse as main transcript	n.696G>A		non_coding_transcript_exon_variant	3/3	2
CBFA2T3	ENST00000563920.1 linkuse as main transcript	n.834G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1403898

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

693180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000462

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.1729G>A (p.G577R) alteration is located in exon 12 (coding exon 12) of the CBFA2T3 gene. This alteration results from a G to A substitution at nucleotide position 1729, causing the glycine (G) at amino acid position 577 to be replaced by an arginine (R). 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

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

.;D

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.86

MutPred

0.60

.;Gain of MoRF binding (P = 0.0245);

MVP

0.60

MPC

1.9

ClinPred

0.99

GERP RS

3.3

Varity_R

0.84

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over