16-88881342-C-G

Variant names:

• chr16-88881342-C-G
• rs371447156
• NM_005187.6:c.1351G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005187.6(CBFA2T3):​c.1351G>C​(p.Ala451Pro) 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)
• Consequence: CBFA2T3 NM_005187.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058490783).

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>C	p.Ala451Pro	missense	Exon 9 of 12	NP_005178.4
	CBFA2T3	NM_175931.3		c.1093G>C	p.Ala365Pro	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.1351G>C	p.Ala451Pro	missense	Exon 9 of 12	ENSP00000268679.4	O75081-1
	CBFA2T3	ENST00000327483.9	TSL:1	c.1093G>C	p.Ala365Pro	missense	Exon 8 of 11	ENSP00000332122.5	O75081-2
	CBFA2T3	ENST00000569464.5	TSL:1	c.1168G>C	p.Ala390Pro	missense	Exon 9 of 10	ENSP00000454851.1	H3BNH2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.072
DANN	Benign	0.38
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		-1.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.027
Sift	Benign	0.36	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.27		Gain of glycosylation at A451 (P = 0.0134)
MVP		0.11
MPC		0.080
ClinPred		0.035	T
GERP RS		-1.2
Varity_R		0.064
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

Other links and lift over

dbSNP: rs371447156; hg19: chr16-88947750;