16-88881306-C-T

Variant names:

• chr16-88881306-C-T
• rs769427504
• NM_005187.6:c.1387G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005187.6(CBFA2T3):​c.1387G>A​(p.Glu463Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,589,238 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: 𝑓 0.000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CBFA2T3 NM_005187.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 1 publications found

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]

ENSG00000259881 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.21995765).

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.1387G>A	p.Glu463Lys	missense	Exon 9 of 12	NP_005178.4
	CBFA2T3	NM_175931.3		c.1129G>A	p.Glu377Lys	missense	Exon 8 of 11	NP_787127.1	O75081-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBFA2T3	ENST00000268679.9	TSL:1 MANE Select	c.1387G>A	p.Glu463Lys	missense	Exon 9 of 12	ENSP00000268679.4	O75081-1
	CBFA2T3	ENST00000327483.9	TSL:1	c.1129G>A	p.Glu377Lys	missense	Exon 8 of 11	ENSP00000332122.5	O75081-2
	CBFA2T3	ENST00000569464.5	TSL:1	c.1204G>A	p.Glu402Lys	missense	Exon 9 of 10	ENSP00000454851.1	H3BNH2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152168 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000548 AC: 12 AN: 218830 AF XY: 0.0000498

Gnomad AFR exome AF: 0.0000732

Gnomad AMR exome AF: 0.0000922

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000716

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 168 AN: 1436952 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 76 AN XY: 712772

African (AFR) AF: 0.0000605 AC: 2 AN: 33034

American (AMR) AF: 0.0000694 AC: 3 AN: 43212

Ashkenazi Jewish (ASJ) AF: 0.0000395 AC: 1 AN: 25338

East Asian (EAS) AF: 0.00 AC: 0 AN: 39140

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.000143 AC: 157 AN: 1101034

Other (OTH) AF: 0.0000675 AC: 4 AN: 59268

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152286 Hom.: 0 Cov.: 34 AF XY: 0.0000940 AC XY: 7 AN XY: 74476

African (AFR) AF: 0.0000241 AC: 1 AN: 41562

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000252 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.028
Eigen_PC	Benign	-0.071
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.073
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.78	P
Vest4		0.59
MutPred		0.36		Gain of ubiquitination at E463 (P = 0.0039)
MVP		0.60
MPC		0.090
ClinPred		0.079	T
GERP RS		4.8
Varity_R		0.16
gMVP		0.50
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs769427504; hg19: chr16-88947714; COSMIC: COSV99240990; COSMIC: COSV99240990;