Genetic Variant CBFA2T3:p.Ala451Ser (chr16-88881342-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005187.6(CBFA2T3):c.1351G>T(p.Ala451Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A451T) has been classified 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

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

1 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:

ENSG00000259881 (HGNC:):

ENSG00000259881 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044537544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005187.6. 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
	CBFA2T3	NM_005187.6	MANE Select	c.1351G>T	p.Ala451Ser	missense	Exon 9 of 12	NP_005178.4
	CBFA2T3	NM_175931.3		c.1093G>T	p.Ala365Ser	missense	Exon 8 of 11	NP_787127.1	O75081-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBFA2T3	ENST00000268679.9	TSL:1 MANE Select	c.1351G>T	p.Ala451Ser	missense	Exon 9 of 12	ENSP00000268679.4	O75081-1
CBFA2T3	ENST00000327483.9	TSL:1	c.1093G>T	p.Ala365Ser	missense	Exon 8 of 11	ENSP00000332122.5	O75081-2
CBFA2T3	ENST00000569464.5	TSL:1	c.1168G>T	p.Ala390Ser	missense	Exon 9 of 10	ENSP00000454851.1	H3BNH2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708842

African (AFR)

AF:

0.00

AC:

AN:

32794

American (AMR)

AF:

0.00

AC:

AN:

41290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25562

East Asian (EAS)

AF:

0.00

AC:

AN:

38202

South Asian (SAS)

AF:

0.00

AC:

AN:

83584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097640

Other (OTH)

AF:

0.00

AC:

AN:

59052

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.042

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.055

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.57

M_CAP

Benign

0.015

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

-1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.11

REVEL

Benign

0.022

Sift

Benign

0.93

Sift4G

Benign

0.85

Polyphen

0.0010

Vest4

0.22

MutPred

0.27

Gain of phosphorylation at A451 (P = 0.0025)

MVP

0.17

MPC

0.060

ClinPred

0.054

GERP RS

-1.2

Varity_R

0.041

gMVP

0.22

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over