Variant chr16-88877026-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005187.6(CBFA2T3):c.1912C>T(p.Arg638Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,338,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CBFA2T3
NM_005187.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10819495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBFA2T3	NM_005187.6 linkuse as main transcript	c.1912C>T	p.Arg638Cys	missense_variant	12/12	ENST00000268679.9	NP_005178.4	O75081-1
CBFA2T3	NM_175931.3 linkuse as main transcript	c.1654C>T	p.Arg552Cys	missense_variant	11/11		NP_787127.1	O75081-2
CBFA2T3	XM_005256323.6 linkuse as main transcript	c.1837C>T	p.Arg613Cys	missense_variant	11/11		XP_005256380.1
CBFA2T3	XM_047434826.1 linkuse as main transcript	c.*1251C>T		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.1912C>T	p.Arg638Cys	missense_variant	12/12	1	NM_005187.6	ENSP00000268679.4	O75081-1
CBFA2T3	ENST00000327483.9 linkuse as main transcript	c.1654C>T	p.Arg552Cys	missense_variant	11/11	1		ENSP00000332122.5	O75081-2
CBFA2T3	ENST00000563856.1 linkuse as main transcript	n.879C>T		non_coding_transcript_exon_variant	3/3	2
CBFA2T3	ENST00000563920.1 linkuse as main transcript	n.1017C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000988

AC:

AN:

101202

Hom.:

AF XY:

0.00

AC XY:

AN XY:

55946

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000747

AC:

AN:

1338682

Hom.:

Cov.:

AF XY:

0.00000305

AC XY:

AN XY:

656138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000344

Gnomad4 AMR exome

AF:

0.0000364

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000290

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000663

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jan 09, 2024

The c.1912C>T (p.R638C) alteration is located in exon 12 (coding exon 12) of the CBFA2T3 gene. This alteration results from a C to T substitution at nucleotide position 1912, causing the arginine (R) at amino acid position 638 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.57

.;D

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.79

T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

.;L

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.066

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.0030

B;B

Vest4

0.14

MVP

0.48

MPC

0.97

ClinPred

0.17

GERP RS

3.1

Varity_R

0.24

gMVP

0.44

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

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