16-88877026-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R638L) has been classified 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

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:

Genome browser will be placed here

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=0.10819495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBFA2T3	NM_005187.6 link	c.1912C>T	p.Arg638Cys	missense_variant	Exon 12 of 12	ENST00000268679.9	NP_005178.4	O75081-1
CBFA2T3	NM_175931.3 link	c.1654C>T	p.Arg552Cys	missense_variant	Exon 11 of 11		NP_787127.1	O75081-2
CBFA2T3	XM_005256323.6 link	c.1837C>T	p.Arg613Cys	missense_variant	Exon 11 of 11		XP_005256380.1
CBFA2T3	XM_047434826.1 link	c.*1251C>T		3_prime_UTR_variant	Exon 11 of 11		XP_047290782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CBFA2T3	ENST00000268679.9 link	c.1912C>T	p.Arg638Cys	missense_variant	Exon 12 of 12	1	NM_005187.6	ENSP00000268679.4	O75081-1
CBFA2T3	ENST00000327483.9 link	c.1654C>T	p.Arg552Cys	missense_variant	Exon 11 of 11	1		ENSP00000332122.5	O75081-2
CBFA2T3	ENST00000563856.1 link	n.879C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
CBFA2T3	ENST00000563920.1 link	n.1017C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000988

AC:

AN:

101202

AF XY:

0.00

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 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

African (AFR)

AF:

0.0000344

AC:

AN:

29088

American (AMR)

AF:

0.0000364

AC:

AN:

27508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22570

East Asian (EAS)

AF:

0.0000290

AC:

AN:

34486

South Asian (SAS)

AF:

0.00

AC:

AN:

73274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3986

European-Non Finnish (NFE)

AF:

0.00000663

AC:

AN:

1055920

Other (OTH)

AF:

0.00

AC:

AN:

55506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

Jan 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

1.1

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

Mutation Taster

=81/19

polymorphism

(source)

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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16-88877026-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over